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Published in: Seminars in Immunopathology 1/2021

01-02-2021 | Review

Dynamics of thymus function and T cell receptor repertoire breadth in health and disease

Authors: David Granadier, Lorenzo Iovino, Sinéad Kinsella, Jarrod A. Dudakov

Published in: Seminars in Immunopathology | Issue 1/2021

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Abstract

T cell recognition of unknown antigens relies on the tremendous diversity of the T cell receptor (TCR) repertoire; generation of which can only occur in the thymus. TCR repertoire breadth is thus critical for not only coordinating the adaptive response against pathogens but also for mounting a response against malignancies. However, thymic function is exquisitely sensitive to negative stimuli, which can come in the form of acute insult, such as that caused by stress, infection, or common cancer therapies; or chronic damage such as the progressive decline in thymic function with age. Whether it be prolonged T cell deficiency after hematopoietic cell transplantation (HCT) or constriction in the breadth of the peripheral TCR repertoire with age; these insults result in poor adaptive immune responses. In this review, we will discuss the importance of thymic function for generation of the TCR repertoire and how acute and chronic thymic damage influences immune health. We will also discuss methods that are used to measure thymic function in patients and strategies that have been developed to boost thymic function.
Literature
1.
go back to reference Huda MN et al (2019) Infant cortisol stress-response is associated with thymic function and vaccine response. Stress 22:36–43PubMedCrossRef Huda MN et al (2019) Infant cortisol stress-response is associated with thymic function and vaccine response. Stress 22:36–43PubMedCrossRef
2.
go back to reference Ashwell JD, Lu FW, Vacchio MS (2000) Glucocorticoids in T cell development and function*. Annu Rev Immunol 18:309–345PubMedCrossRef Ashwell JD, Lu FW, Vacchio MS (2000) Glucocorticoids in T cell development and function*. Annu Rev Immunol 18:309–345PubMedCrossRef
3.
go back to reference Purton JF et al (2004) Expression of the glucocorticoid receptor from the 1A promoter correlates with T lymphocyte sensitivity to glucocorticoid-induced cell death. J Immunol 173:3816–3824CrossRefPubMed Purton JF et al (2004) Expression of the glucocorticoid receptor from the 1A promoter correlates with T lymphocyte sensitivity to glucocorticoid-induced cell death. J Immunol 173:3816–3824CrossRefPubMed
5.
go back to reference Calder AE, Hince MN, Dudakov JA, Chidgey AP, Boyd RL (2011) Thymic involution: where endocrinology meets immunology. Neuroimmunomodulation 18:281–289PubMedCrossRef Calder AE, Hince MN, Dudakov JA, Chidgey AP, Boyd RL (2011) Thymic involution: where endocrinology meets immunology. Neuroimmunomodulation 18:281–289PubMedCrossRef
6.
go back to reference Paolino M et al (2020) RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy. Nature Paolino M et al (2020) RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy. Nature
7.
go back to reference Vezys V et al (2006) Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J Exp Med 203:2263–2269PubMedPubMedCentralCrossRef Vezys V et al (2006) Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J Exp Med 203:2263–2269PubMedPubMedCentralCrossRef
8.
go back to reference Miller NE, Bonczyk JR, Nakayama Y, Suresh M (2005) Role of thymic output in regulating CD8 T cell homeostasis during acute and chronic viral infection. J Virol 79:9419–9429PubMedPubMedCentralCrossRef Miller NE, Bonczyk JR, Nakayama Y, Suresh M (2005) Role of thymic output in regulating CD8 T cell homeostasis during acute and chronic viral infection. J Virol 79:9419–9429PubMedPubMedCentralCrossRef
10.
go back to reference Wang S et al (2020) Streptococcus suis serotype 2 infection causes host immunomodulation through induction of thymic atrophy. Infect Immun 88:e00950–e00919PubMedPubMedCentral Wang S et al (2020) Streptococcus suis serotype 2 infection causes host immunomodulation through induction of thymic atrophy. Infect Immun 88:e00950–e00919PubMedPubMedCentral
11.
go back to reference Reiley WW et al (2012) Maintenance of peripheral T cell responses during Mycobacterium tuberculosis infection. J Immunol 189:4451–4458PubMedCrossRef Reiley WW et al (2012) Maintenance of peripheral T cell responses during Mycobacterium tuberculosis infection. J Immunol 189:4451–4458PubMedCrossRef
12.
go back to reference D'Attilio L, Santucci N, Bongiovanni B, Bay ML, Bottasso O (2018) Tuberculosis, the disrupted immune-endocrine response and the potential thymic repercussion as a contributing factor to disease physiopathology. Front Endocrinol (Lausanne) 9:214CrossRef D'Attilio L, Santucci N, Bongiovanni B, Bay ML, Bottasso O (2018) Tuberculosis, the disrupted immune-endocrine response and the potential thymic repercussion as a contributing factor to disease physiopathology. Front Endocrinol (Lausanne) 9:214CrossRef
13.
go back to reference Small TN et al (1997) Immune reconstitution following T cell depleted bone marrow transplantation: effect of age and posttransplant graft rejection prophylaxis. Biol Blood Marrow Transplant 3:65–75PubMed Small TN et al (1997) Immune reconstitution following T cell depleted bone marrow transplantation: effect of age and posttransplant graft rejection prophylaxis. Biol Blood Marrow Transplant 3:65–75PubMed
14.
go back to reference Bosch M, Khan FM, Storek J (2012) Immune reconstitution after hematopoietic cell transplantation. Curr Opin Hematol 19:324–335PubMedCrossRef Bosch M, Khan FM, Storek J (2012) Immune reconstitution after hematopoietic cell transplantation. Curr Opin Hematol 19:324–335PubMedCrossRef
17.
go back to reference Gray DH et al (2006) Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 108:3777–3785PubMedCrossRef Gray DH et al (2006) Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 108:3777–3785PubMedCrossRef
18.
go back to reference Mackall CL et al (1995) Age, thymopoiesis, and CD4+ T lymphocyte regeneration after intensive chemotherapy. N Engl J Med 332:143–149CrossRefPubMed Mackall CL et al (1995) Age, thymopoiesis, and CD4+ T lymphocyte regeneration after intensive chemotherapy. N Engl J Med 332:143–149CrossRefPubMed
19.
go back to reference Sykes M, Szot GL, Swenson K, Pearson DA, Wekerle T (1998) Separate regulation of peripheral hematopoietic and thymic engraftment. Exp Hematol 26:457–465PubMed Sykes M, Szot GL, Swenson K, Pearson DA, Wekerle T (1998) Separate regulation of peripheral hematopoietic and thymic engraftment. Exp Hematol 26:457–465PubMed
20.
go back to reference Dudakov JA et al (2009) Sex steroid ablation enhances hematopoietic recovery following cytotoxic antineoplastic therapy in aged mice. J Immunol 183:7084–7094PubMedCrossRef Dudakov JA et al (2009) Sex steroid ablation enhances hematopoietic recovery following cytotoxic antineoplastic therapy in aged mice. J Immunol 183:7084–7094PubMedCrossRef
21.
go back to reference Parkman R, Weinberg KI (1997) Immunological reconstitution following bone marrow transplantation. Immunol Rev 157:73–78PubMedCrossRef Parkman R, Weinberg KI (1997) Immunological reconstitution following bone marrow transplantation. Immunol Rev 157:73–78PubMedCrossRef
22.
go back to reference Weinberg K et al (1995) The effect of thymic function on immunocompetence following bone marrow transplantation. Biol Blood Marrow Transplant 1:18–23PubMed Weinberg K et al (1995) The effect of thymic function on immunocompetence following bone marrow transplantation. Biol Blood Marrow Transplant 1:18–23PubMed
23.
go back to reference Komanduri KV et al (2007) Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T cell skewing. Blood 110:4543–4551PubMedPubMedCentralCrossRef Komanduri KV et al (2007) Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T cell skewing. Blood 110:4543–4551PubMedPubMedCentralCrossRef
24.
go back to reference Legrand N, Dontje W, van Lent AU, Spits H, Blom B (2007) Human thymus regeneration and T cell reconstitution. Semin Immunol 19:280–288PubMedCrossRef Legrand N, Dontje W, van Lent AU, Spits H, Blom B (2007) Human thymus regeneration and T cell reconstitution. Semin Immunol 19:280–288PubMedCrossRef
25.
26.
go back to reference Storek J et al (2001) Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation. Blood 98:3505–3512PubMedCrossRef Storek J et al (2001) Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation. Blood 98:3505–3512PubMedCrossRef
27.
go back to reference Maury S et al (2001) Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients. Br J Haematol 115:630–641PubMedCrossRef Maury S et al (2001) Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients. Br J Haematol 115:630–641PubMedCrossRef
28.
go back to reference Storek J, Gooley T, Witherspoon RP, Sullivan KM, Storb R (1997) Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts. Am J Hematol 54:131–138PubMedCrossRef Storek J, Gooley T, Witherspoon RP, Sullivan KM, Storb R (1997) Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts. Am J Hematol 54:131–138PubMedCrossRef
29.
go back to reference Fletcher AL et al (2009) Ablation and regeneration of tolerance-inducing medullary thymic epithelial cells after cyclosporine, cyclophosphamide, and dexamethasone treatment. J Immunol 183:823–831PubMedCrossRef Fletcher AL et al (2009) Ablation and regeneration of tolerance-inducing medullary thymic epithelial cells after cyclosporine, cyclophosphamide, and dexamethasone treatment. J Immunol 183:823–831PubMedCrossRef
30.
go back to reference Na I-K et al (2010) The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease. J Clin Invest 120:343–356PubMedCrossRef Na I-K et al (2010) The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease. J Clin Invest 120:343–356PubMedCrossRef
31.
32.
go back to reference Krenger W, Rossi S, Hollander GA (2000) Apoptosis of thymocytes during acute graft-versus-host disease is independent of glucocorticoids. Transplantation 69:2190–2193PubMedCrossRef Krenger W, Rossi S, Hollander GA (2000) Apoptosis of thymocytes during acute graft-versus-host disease is independent of glucocorticoids. Transplantation 69:2190–2193PubMedCrossRef
33.
go back to reference Dudakov JA et al (2017) Loss of thymic innate lymphoid cells leads to impaired thymopoiesis in experimental graft-versus-host disease. Blood 130:933–942PubMedPubMedCentralCrossRef Dudakov JA et al (2017) Loss of thymic innate lymphoid cells leads to impaired thymopoiesis in experimental graft-versus-host disease. Blood 130:933–942PubMedPubMedCentralCrossRef
34.
go back to reference Dertschnig S, Hauri-Hohl MM, Vollmer M, Holländer GA, Krenger W (2015) Impaired thymic expression of tissue-restricted antigens licenses the de novo generation of autoreactive CD4+ T cells in acute GVHD. Blood 125:2720–2723PubMedPubMedCentralCrossRef Dertschnig S, Hauri-Hohl MM, Vollmer M, Holländer GA, Krenger W (2015) Impaired thymic expression of tissue-restricted antigens licenses the de novo generation of autoreactive CD4+ T cells in acute GVHD. Blood 125:2720–2723PubMedPubMedCentralCrossRef
35.
go back to reference Hollander GA, Widmer B, Burakoff SJ (1994) Loss of normal thymic repertoire selection and persistence of autoreactive T cells in graft vs host disease. J Immunol 152:1609–1617PubMed Hollander GA, Widmer B, Burakoff SJ (1994) Loss of normal thymic repertoire selection and persistence of autoreactive T cells in graft vs host disease. J Immunol 152:1609–1617PubMed
36.
go back to reference Wu T et al (2013) Thymic damage, impaired negative selection, and development of chronic graft-versus-host disease caused by donor CD4+ and CD8+ T cells. J Immunol 191:488–499PubMedCrossRef Wu T et al (2013) Thymic damage, impaired negative selection, and development of chronic graft-versus-host disease caused by donor CD4+ and CD8+ T cells. J Immunol 191:488–499PubMedCrossRef
37.
go back to reference Su L et al (1995) HIV-1-induced thymocyte depletion is associated with indirect cytopathogenicity and infection of progenitor cells in vivo. Immunity 2:25–36PubMedCrossRef Su L et al (1995) HIV-1-induced thymocyte depletion is associated with indirect cytopathogenicity and infection of progenitor cells in vivo. Immunity 2:25–36PubMedCrossRef
38.
go back to reference Calabro ML et al (1995) HIV-1 infection of the thymus: evidence for a cytopathic and thymotropic viral variant in vivo. AIDS Res Hum Retrovir 11:11–19PubMedCrossRef Calabro ML et al (1995) HIV-1 infection of the thymus: evidence for a cytopathic and thymotropic viral variant in vivo. AIDS Res Hum Retrovir 11:11–19PubMedCrossRef
40.
41.
go back to reference Nikolich-Zugich J, Slifka MK, Messaoudi I (2004) The many important facets of T cell repertoire diversity. Nat Rev Immunol 4:123–132PubMedCrossRef Nikolich-Zugich J, Slifka MK, Messaoudi I (2004) The many important facets of T cell repertoire diversity. Nat Rev Immunol 4:123–132PubMedCrossRef
42.
go back to reference Sandgaard KS, Lewis J, Adams S, Klein N, Callard R (2014) Antiretroviral therapy increases thymic output in children with HIV. Aids 28:209–214PubMedCrossRef Sandgaard KS, Lewis J, Adams S, Klein N, Callard R (2014) Antiretroviral therapy increases thymic output in children with HIV. Aids 28:209–214PubMedCrossRef
43.
go back to reference Fernandez S et al (2006) Thymic function in severely immunodeficient HIV type 1-infected patients receiving stable and effective antiretroviral therapy. AIDS Res Hum Retrovir 22:163–170PubMedCrossRef Fernandez S et al (2006) Thymic function in severely immunodeficient HIV type 1-infected patients receiving stable and effective antiretroviral therapy. AIDS Res Hum Retrovir 22:163–170PubMedCrossRef
44.
go back to reference Rb-Silva R et al (2019) Thymic function as a predictor of immune recovery in chronically HIV-infected patients initiating antiretroviral therapy. Front Immunol 10:25PubMedPubMedCentralCrossRef Rb-Silva R et al (2019) Thymic function as a predictor of immune recovery in chronically HIV-infected patients initiating antiretroviral therapy. Front Immunol 10:25PubMedPubMedCentralCrossRef
45.
go back to reference Zakhour R et al (2016) Recent thymus emigrant CD4+ T cells predict HIV disease progression in patients with perinatally acquired HIV. Clin Infect Dis 62:1029–1035PubMedPubMedCentralCrossRef Zakhour R et al (2016) Recent thymus emigrant CD4+ T cells predict HIV disease progression in patients with perinatally acquired HIV. Clin Infect Dis 62:1029–1035PubMedPubMedCentralCrossRef
46.
go back to reference Trautmann L et al (2005) Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. J Immunol 175:6123–6132PubMedCrossRef Trautmann L et al (2005) Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. J Immunol 175:6123–6132PubMedCrossRef
47.
go back to reference Argaet VP et al (1994) Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus. J Exp Med 180:2335–2340PubMedCrossRef Argaet VP et al (1994) Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus. J Exp Med 180:2335–2340PubMedCrossRef
48.
go back to reference Miyasaka A, Yoshida Y, Wang T, Takikawa Y (2019) Next-generation sequencing analysis of the human T cell and B cell receptor repertoire diversity before and after hepatitis B vaccination. Hum Vaccin Immunother 15:2738–2753PubMedPubMedCentralCrossRef Miyasaka A, Yoshida Y, Wang T, Takikawa Y (2019) Next-generation sequencing analysis of the human T cell and B cell receptor repertoire diversity before and after hepatitis B vaccination. Hum Vaccin Immunother 15:2738–2753PubMedPubMedCentralCrossRef
50.
go back to reference Drabkin MJ et al (2018) Age-stratified patterns of thymic involution on multidetector CT. J Thorac Imaging 33:409–416PubMedCrossRef Drabkin MJ et al (2018) Age-stratified patterns of thymic involution on multidetector CT. J Thorac Imaging 33:409–416PubMedCrossRef
52.
go back to reference Rezzani R, Nardo L, Favero G, Peroni M, Rodella LF (2014) Thymus and aging: morphological, radiological, and functional overview. Age (Dordr) 36:313–351CrossRef Rezzani R, Nardo L, Favero G, Peroni M, Rodella LF (2014) Thymus and aging: morphological, radiological, and functional overview. Age (Dordr) 36:313–351CrossRef
53.
go back to reference Posnett DN et al (2003) Oligoclonal expansions of antigen-specific CD8+ T cells in aged mice. Ann N Y Acad Sci 987:274–279PubMedCrossRef Posnett DN et al (2003) Oligoclonal expansions of antigen-specific CD8+ T cells in aged mice. Ann N Y Acad Sci 987:274–279PubMedCrossRef
54.
go back to reference Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5:133–139PubMedCrossRef Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5:133–139PubMedCrossRef
55.
go back to reference Cicin-Sain L et al (2010) Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates. J Immunol 184:6739–6745PubMedCrossRef Cicin-Sain L et al (2010) Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates. J Immunol 184:6739–6745PubMedCrossRef
56.
go back to reference Coder BD, Wang H, Ruan L, Su DM (2015) Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation. J Immunol 194:5825–5837PubMedCrossRef Coder BD, Wang H, Ruan L, Su DM (2015) Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation. J Immunol 194:5825–5837PubMedCrossRef
57.
go back to reference Xia J et al (2012) Age-related disruption of steady-state thymic medulla provokes autoimmune phenotype via perturbing negative selection. Aging Dis 3:248–259PubMedPubMedCentral Xia J et al (2012) Age-related disruption of steady-state thymic medulla provokes autoimmune phenotype via perturbing negative selection. Aging Dis 3:248–259PubMedPubMedCentral
58.
go back to reference Tyan ML (1977) Age-related decrease in mouse T cell progenitors. J Immunol 118:846–851PubMed Tyan ML (1977) Age-related decrease in mouse T cell progenitors. J Immunol 118:846–851PubMed
59.
go back to reference Hirokawa K, Kubo S, Utsuyama M, Kurashima C, Sado T (1986) Age-related change in the potential of bone marrow cells to repopulate the thymus and splenic T cells in mice. Cell Immunol 100:443–451PubMedCrossRef Hirokawa K, Kubo S, Utsuyama M, Kurashima C, Sado T (1986) Age-related change in the potential of bone marrow cells to repopulate the thymus and splenic T cells in mice. Cell Immunol 100:443–451PubMedCrossRef
60.
go back to reference Heng TS et al (2005) Effects of castration on thymocyte development in two different models of thymic involution. J Immunol 175:2982–2993PubMedCrossRef Heng TS et al (2005) Effects of castration on thymocyte development in two different models of thymic involution. J Immunol 175:2982–2993PubMedCrossRef
62.
go back to reference Gui J et al (2007) The aged thymus shows normal recruitment of lymphohematopoietic progenitors but has defects in thymic epithelial cells. Int Immunol 19:1201–1211PubMedCrossRef Gui J et al (2007) The aged thymus shows normal recruitment of lymphohematopoietic progenitors but has defects in thymic epithelial cells. Int Immunol 19:1201–1211PubMedCrossRef
63.
go back to reference Dudakov JA, Khong DMP, Boyd RL, Chidgey AP (2010) Feeding the fire: the role of defective bone marrow function in exacerbating thymic involution. Trends Immunol 31:191–198PubMedCrossRef Dudakov JA, Khong DMP, Boyd RL, Chidgey AP (2010) Feeding the fire: the role of defective bone marrow function in exacerbating thymic involution. Trends Immunol 31:191–198PubMedCrossRef
64.
go back to reference Ortman CL, Dittmar KA, Witte PL, Le PT (2002) Molecular characterization of the mouse involuted thymus: aberrations in expression of transcription regulators in thymocyte and epithelial compartments. Int Immunol 14:813–822PubMedCrossRef Ortman CL, Dittmar KA, Witte PL, Le PT (2002) Molecular characterization of the mouse involuted thymus: aberrations in expression of transcription regulators in thymocyte and epithelial compartments. Int Immunol 14:813–822PubMedCrossRef
65.
go back to reference Aw D, Silva AB, Maddick M, von Zglinicki T, Palmer DB (2008) Architectural changes in the thymus of aging mice. Aging Cell 7:158–167PubMedCrossRef Aw D, Silva AB, Maddick M, von Zglinicki T, Palmer DB (2008) Architectural changes in the thymus of aging mice. Aging Cell 7:158–167PubMedCrossRef
67.
go back to reference Palmer S, Albergante L, Blackburn CC, Newman TJ (2018) Thymic involution and rising disease incidence with age. Proc Natl Acad Sci U S A 115:1883–1888PubMedPubMedCentralCrossRef Palmer S, Albergante L, Blackburn CC, Newman TJ (2018) Thymic involution and rising disease incidence with age. Proc Natl Acad Sci U S A 115:1883–1888PubMedPubMedCentralCrossRef
69.
go back to reference Handel AE, Irani SR, Hollander GA (2018) The role of thymic tolerance in CNS autoimmune disease. Nat Rev Neurol 14:723–734PubMedCrossRef Handel AE, Irani SR, Hollander GA (2018) The role of thymic tolerance in CNS autoimmune disease. Nat Rev Neurol 14:723–734PubMedCrossRef
70.
72.
go back to reference Goldberg GL et al (2010) Sex steroid ablation enhances immune reconstitution following cytotoxic antineoplastic therapy in young mice. J Immunol 184:6014–6024PubMedCrossRef Goldberg GL et al (2010) Sex steroid ablation enhances immune reconstitution following cytotoxic antineoplastic therapy in young mice. J Immunol 184:6014–6024PubMedCrossRef
73.
go back to reference Jaffe HL (1924) The influence of the suprarenal gland on the thymus : I Regeneration of the thymus following double suprarenalectomy in the rat. J Exp Med 40:325–342PubMedPubMedCentralCrossRef Jaffe HL (1924) The influence of the suprarenal gland on the thymus : I Regeneration of the thymus following double suprarenalectomy in the rat. J Exp Med 40:325–342PubMedPubMedCentralCrossRef
75.
go back to reference Chidgey A, Dudakov J, Seach N, Boyd R (2007) Impact of niche aging on thymic regeneration and immune reconstitution. Semin Immunol 19:331–340PubMedCrossRef Chidgey A, Dudakov J, Seach N, Boyd R (2007) Impact of niche aging on thymic regeneration and immune reconstitution. Semin Immunol 19:331–340PubMedCrossRef
76.
go back to reference Pan B et al (2014) Acute ablation of DP thymocytes induces up-regulation of IL-22 and Foxn1 in TECs. Clin Immunol 150:101–108PubMedCrossRef Pan B et al (2014) Acute ablation of DP thymocytes induces up-regulation of IL-22 and Foxn1 in TECs. Clin Immunol 150:101–108PubMedCrossRef
78.
go back to reference Hikosaka Y et al (2008) The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity 29:438–450PubMedCrossRef Hikosaka Y et al (2008) The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity 29:438–450PubMedCrossRef
79.
go back to reference Roberts NA et al (2012) Rank signaling links the development of invariant gammadelta T cell progenitors and Aire(+) medullary epithelium. Immunity 36:427–437PubMedPubMedCentralCrossRef Roberts NA et al (2012) Rank signaling links the development of invariant gammadelta T cell progenitors and Aire(+) medullary epithelium. Immunity 36:427–437PubMedPubMedCentralCrossRef
80.
go back to reference Rossi SW et al (2007) RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med 204:1267–1272PubMedPubMedCentralCrossRef Rossi SW et al (2007) RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med 204:1267–1272PubMedPubMedCentralCrossRef
81.
go back to reference Lopes N, Vachon H, Marie J, Irla M (2017) Administration of RANKL boosts thymic regeneration upon bone marrow transplantation. EMBO Mol Med 9:835–851PubMedPubMedCentralCrossRef Lopes N, Vachon H, Marie J, Irla M (2017) Administration of RANKL boosts thymic regeneration upon bone marrow transplantation. EMBO Mol Med 9:835–851PubMedPubMedCentralCrossRef
82.
go back to reference Akiyama T et al (2008) The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 29:423–437PubMedCrossRef Akiyama T et al (2008) The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 29:423–437PubMedCrossRef
84.
go back to reference Akiyama T et al (2005) Dependence of self-tolerance on TRAF6-directed development of thymic stroma. Science 308:248–251PubMedCrossRef Akiyama T et al (2005) Dependence of self-tolerance on TRAF6-directed development of thymic stroma. Science 308:248–251PubMedCrossRef
86.
go back to reference Ohigashi I, Nitta T, Lkhagvasuren E, Yasuda H, Takahama Y (2011) Effects of RANKL on the thymic medulla. Eur J Immunol 41:1822–1827PubMedCrossRef Ohigashi I, Nitta T, Lkhagvasuren E, Yasuda H, Takahama Y (2011) Effects of RANKL on the thymic medulla. Eur J Immunol 41:1822–1827PubMedCrossRef
87.
go back to reference McCarthy NI et al (2015) Osteoprotegerin-mediated homeostasis of rank+ thymic epithelial cells does not limit Foxp3+ regulatory T cell development. J Immunol 195:2675–2682PubMedPubMedCentralCrossRef McCarthy NI et al (2015) Osteoprotegerin-mediated homeostasis of rank+ thymic epithelial cells does not limit Foxp3+ regulatory T cell development. J Immunol 195:2675–2682PubMedPubMedCentralCrossRef
88.
go back to reference Lo Iacono N et al (2012) Osteopetrosis rescue upon RANKL administration to Rankl(-/-) mice: a new therapy for human RANKL-dependent ARO. J Bone Miner Res 27:2501–2510PubMedCrossRef Lo Iacono N et al (2012) Osteopetrosis rescue upon RANKL administration to Rankl(-/-) mice: a new therapy for human RANKL-dependent ARO. J Bone Miner Res 27:2501–2510PubMedCrossRef
89.
go back to reference Bleul CC, Boehm T (2005) BMP signaling is required for normal thymus development. J Immunol 175:5213–5221PubMedCrossRef Bleul CC, Boehm T (2005) BMP signaling is required for normal thymus development. J Immunol 175:5213–5221PubMedCrossRef
90.
go back to reference Patel SR, Gordon J, Mahbub F, Blackburn CC, Manley NR (2006) Bmp4 and Noggin expression during early thymus and parathyroid organogenesis. Gene Expr Patterns 6:794–799PubMedCrossRef Patel SR, Gordon J, Mahbub F, Blackburn CC, Manley NR (2006) Bmp4 and Noggin expression during early thymus and parathyroid organogenesis. Gene Expr Patterns 6:794–799PubMedCrossRef
91.
go back to reference Gordon J, Patel SR, Mishina Y, Manley NR (2010) Evidence for an early role for BMP4 signaling in thymus and parathyroid morphogenesis. Dev Biol 339:141–154PubMedPubMedCentralCrossRef Gordon J, Patel SR, Mishina Y, Manley NR (2010) Evidence for an early role for BMP4 signaling in thymus and parathyroid morphogenesis. Dev Biol 339:141–154PubMedPubMedCentralCrossRef
92.
go back to reference Parent AV et al (2013) Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development. Cell Stem Cell 13:219–229PubMedCrossRef Parent AV et al (2013) Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development. Cell Stem Cell 13:219–229PubMedCrossRef
93.
go back to reference Sun X et al (2013) Directed differentiation of human embryonic stem cells into thymic epithelial progenitor-like cells reconstitutes the thymic microenvironment in†vivo. Cell Stem Cell 13:230–236PubMedCrossRef Sun X et al (2013) Directed differentiation of human embryonic stem cells into thymic epithelial progenitor-like cells reconstitutes the thymic microenvironment in†vivo. Cell Stem Cell 13:230–236PubMedCrossRef
94.
go back to reference Soh C-L et al (2014) FOXN1GFP/w reporter hESCs enable identification of integrin-β4, HLA-DR, and EpCAM as markers of human PSC-derived FOXN1+ thymic epithelial progenitors. Stem Cell Rep 2:925–937CrossRef Soh C-L et al (2014) FOXN1GFP/w reporter hESCs enable identification of integrin-β4, HLA-DR, and EpCAM as markers of human PSC-derived FOXN1+ thymic epithelial progenitors. Stem Cell Rep 2:925–937CrossRef
97.
go back to reference Rossi SW et al (2007) Keratinocyte growth factor (KGF) enhances postnatal T cell development via enhancements in proliferation and function of thymic epithelial cells. Blood 109:3803–3811PubMedPubMedCentralCrossRef Rossi SW et al (2007) Keratinocyte growth factor (KGF) enhances postnatal T cell development via enhancements in proliferation and function of thymic epithelial cells. Blood 109:3803–3811PubMedPubMedCentralCrossRef
98.
go back to reference Rossi S et al (2002) Keratinocyte growth factor preserves normal thymopoiesis and thymic microenvironment during experimental graft-versus-host disease. Blood 100:682–691PubMedCrossRef Rossi S et al (2002) Keratinocyte growth factor preserves normal thymopoiesis and thymic microenvironment during experimental graft-versus-host disease. Blood 100:682–691PubMedCrossRef
99.
go back to reference Porrata LF et al (2001) Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non- Hodgkin lymphoma. Blood 98:579–585PubMedCrossRef Porrata LF et al (2001) Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non- Hodgkin lymphoma. Blood 98:579–585PubMedCrossRef
100.
go back to reference Le Blanc K et al (2009) Lymphocyte recovery is a major determinant of outcome after matched unrelated myeloablative transplantation for myelogenous malignancies. Biol Blood Marrow Transplant 15:1108–1115PubMedPubMedCentralCrossRef Le Blanc K et al (2009) Lymphocyte recovery is a major determinant of outcome after matched unrelated myeloablative transplantation for myelogenous malignancies. Biol Blood Marrow Transplant 15:1108–1115PubMedPubMedCentralCrossRef
101.
go back to reference Savani BN et al (2007) Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation. Biol Blood Marrow Transplant 13:1216–1223PubMedPubMedCentralCrossRef Savani BN et al (2007) Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation. Biol Blood Marrow Transplant 13:1216–1223PubMedPubMedCentralCrossRef
102.
go back to reference Chakrabarti S et al (2003) Early lymphocyte recovery is an important determinant of outcome following allogeneic transplantation with CD34+ selected graft and limited T cell addback. Bone Marrow Transplant 32:23–30PubMedCrossRef Chakrabarti S et al (2003) Early lymphocyte recovery is an important determinant of outcome following allogeneic transplantation with CD34+ selected graft and limited T cell addback. Bone Marrow Transplant 32:23–30PubMedCrossRef
103.
go back to reference Burke MJ et al (2011) Early lymphocyte recovery and outcomes after umbilical cord blood transplantation (UCBT) for hematologic malignancies. Biol Blood Marrow Transplant 17:831–840PubMedCrossRef Burke MJ et al (2011) Early lymphocyte recovery and outcomes after umbilical cord blood transplantation (UCBT) for hematologic malignancies. Biol Blood Marrow Transplant 17:831–840PubMedCrossRef
104.
go back to reference Varga I, Uhrinova A, Toth F, Mistinova J (2011) Assessment of the thymic morphometry using ultrasound in full-term newborns. Surg Radiol Anat: SRA 33:689–695PubMedCrossRef Varga I, Uhrinova A, Toth F, Mistinova J (2011) Assessment of the thymic morphometry using ultrasound in full-term newborns. Surg Radiol Anat: SRA 33:689–695PubMedCrossRef
105.
go back to reference Tonni G et al (2016) Fetal thymus: visualization rate and volume by integrating 2D- and 3D-ultrasound during 2nd trimester echocardiography. J Matern-Fetal Neonatal Med : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 29:2223–2228CrossRef Tonni G et al (2016) Fetal thymus: visualization rate and volume by integrating 2D- and 3D-ultrasound during 2nd trimester echocardiography. J Matern-Fetal Neonatal Med : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 29:2223–2228CrossRef
106.
go back to reference Ramachandran R, Babu SR, Ilanchezhian S, Radhakrishnan PR (2015) Role of imaging and cytogenetics in evaluation of DiGeorge syndrome - a rare entity in clinical practice. J Clin Imaging Sci 5:4PubMedPubMedCentralCrossRef Ramachandran R, Babu SR, Ilanchezhian S, Radhakrishnan PR (2015) Role of imaging and cytogenetics in evaluation of DiGeorge syndrome - a rare entity in clinical practice. J Clin Imaging Sci 5:4PubMedPubMedCentralCrossRef
107.
go back to reference Kerpel A, Beytelman A, Ofek E, Marom EM (2019) Magnetic resonance imaging for the follow-up of treated thymic epithelial malignancies. J Thorac Imaging 34:345–350PubMedCrossRef Kerpel A, Beytelman A, Ofek E, Marom EM (2019) Magnetic resonance imaging for the follow-up of treated thymic epithelial malignancies. J Thorac Imaging 34:345–350PubMedCrossRef
108.
go back to reference Chen CH et al (2017) Rebound thymic hyperplasia after chemotherapy in children with lymphoma. Pediatr Neonatol 58:151–157PubMedCrossRef Chen CH et al (2017) Rebound thymic hyperplasia after chemotherapy in children with lymphoma. Pediatr Neonatol 58:151–157PubMedCrossRef
109.
go back to reference Guida M et al (2013) Mediastinal mass following successful chemotherapy for ovary dysgerminoma: benign process or disease relapse? A case report. J Pediatr Adolesc Gynecol 26:e13–e16PubMedCrossRef Guida M et al (2013) Mediastinal mass following successful chemotherapy for ovary dysgerminoma: benign process or disease relapse? A case report. J Pediatr Adolesc Gynecol 26:e13–e16PubMedCrossRef
110.
go back to reference Sun DP et al (2016) Thymic hyperplasia after chemotherapy in adults with mature B cell lymphoma and its influence on thymic output and CD4(+) T cells repopulation. Oncoimmunology 5:e1137417PubMedPubMedCentralCrossRef Sun DP et al (2016) Thymic hyperplasia after chemotherapy in adults with mature B cell lymphoma and its influence on thymic output and CD4(+) T cells repopulation. Oncoimmunology 5:e1137417PubMedPubMedCentralCrossRef
111.
go back to reference Jeon TJ, Lee YS, Lee JH, Chang HS, Ryu YH (2014) Rebound thymic hyperplasia detected by 18F-FDG PET/CT after radioactive iodine ablation therapy for thyroid cancer. Thyroid : official journal of the American Thyroid Association 24:1636–1641CrossRef Jeon TJ, Lee YS, Lee JH, Chang HS, Ryu YH (2014) Rebound thymic hyperplasia detected by 18F-FDG PET/CT after radioactive iodine ablation therapy for thyroid cancer. Thyroid : official journal of the American Thyroid Association 24:1636–1641CrossRef
112.
go back to reference Lee JC et al (2006) Thymic volume, T cell populations, and parameters of thymopoiesis in adolescent and adult survivors of HIV infection acquired in infancy. AIDS 20:667–674PubMedCrossRef Lee JC et al (2006) Thymic volume, T cell populations, and parameters of thymopoiesis in adolescent and adult survivors of HIV infection acquired in infancy. AIDS 20:667–674PubMedCrossRef
113.
go back to reference Rosado-Sánchez I et al (2017) Thymic function impacts the peripheral CD4/CD8 ratio of HIV-infected subjects. Clin Infect Dis 64:152–158PubMedCrossRef Rosado-Sánchez I et al (2017) Thymic function impacts the peripheral CD4/CD8 ratio of HIV-infected subjects. Clin Infect Dis 64:152–158PubMedCrossRef
114.
go back to reference L. Story et al, (2020) Antenatal thymus volumes in fetuses that deliver <32 weeks gestation: an MRI pilot study. Acta Obstet Gynecol Scand. L. Story et al, (2020) Antenatal thymus volumes in fetuses that deliver <32 weeks gestation: an MRI pilot study. Acta Obstet Gynecol Scand.
116.
go back to reference Schatz DG, Oettinger MA, Baltimore D (1989) The V(D)J recombination activating gene, RAG-1. Cell 59:1035–1048PubMedCrossRef Schatz DG, Oettinger MA, Baltimore D (1989) The V(D)J recombination activating gene, RAG-1. Cell 59:1035–1048PubMedCrossRef
117.
go back to reference Oettinger MA, Schatz DG, Gorka C, Baltimore D (1990) RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248:1517–1523PubMedCrossRef Oettinger MA, Schatz DG, Gorka C, Baltimore D (1990) RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248:1517–1523PubMedCrossRef
119.
go back to reference Boursalian TE, Golob J, Soper DM, Cooper CJ, Fink PJ (2004) Continued maturation of thymic emigrants in the periphery. Nat Immunol 5:418–425PubMedCrossRef Boursalian TE, Golob J, Soper DM, Cooper CJ, Fink PJ (2004) Continued maturation of thymic emigrants in the periphery. Nat Immunol 5:418–425PubMedCrossRef
120.
go back to reference Kong FK, Chen CL, Six A, Hockett RD, Cooper MD (1999) T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool. Proc Natl Acad Sci U S A 96:1536–1540PubMedPubMedCentralCrossRef Kong FK, Chen CL, Six A, Hockett RD, Cooper MD (1999) T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool. Proc Natl Acad Sci U S A 96:1536–1540PubMedPubMedCentralCrossRef
121.
go back to reference Douek DC et al (1998) Changes in thymic function with age and during the treatment of HIV infection. Nature 396:690–695PubMedCrossRef Douek DC et al (1998) Changes in thymic function with age and during the treatment of HIV infection. Nature 396:690–695PubMedCrossRef
122.
go back to reference Douek DC et al (2000) Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T cell reconstitution. Lancet 355:1875–1881PubMedCrossRef Douek DC et al (2000) Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T cell reconstitution. Lancet 355:1875–1881PubMedCrossRef
123.
go back to reference Hazenberg MD, Borghans JA, de Boer RJ, Miedema F (2003) Thymic output: a bad TREC record. Nat Immunol 4:97–99PubMedCrossRef Hazenberg MD, Borghans JA, de Boer RJ, Miedema F (2003) Thymic output: a bad TREC record. Nat Immunol 4:97–99PubMedCrossRef
124.
go back to reference Verschuren MC et al (1997) Preferential rearrangements of the T cell receptor-delta-deleting elements in human T cells. J Immunol 158:1208–1216PubMed Verschuren MC et al (1997) Preferential rearrangements of the T cell receptor-delta-deleting elements in human T cells. J Immunol 158:1208–1216PubMed
125.
go back to reference Dik WA et al (2005) New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling. J Exp Med 201:1715–1723PubMedPubMedCentralCrossRef Dik WA et al (2005) New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling. J Exp Med 201:1715–1723PubMedPubMedCentralCrossRef
126.
go back to reference van Zelm MC, Szczepanski T, van der Burg M, van Dongen JJ (2007) Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion. J Exp Med 204:645–655PubMedPubMedCentralCrossRef van Zelm MC, Szczepanski T, van der Burg M, van Dongen JJ (2007) Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion. J Exp Med 204:645–655PubMedPubMedCentralCrossRef
127.
go back to reference van der Weerd K et al (2013) Combined TCRG and TCRA TREC analysis reveals increased peripheral T lymphocyte but constant intra-thymic proliferative history upon ageing. Mol Immunol 53:302–312PubMedCrossRef van der Weerd K et al (2013) Combined TCRG and TCRA TREC analysis reveals increased peripheral T lymphocyte but constant intra-thymic proliferative history upon ageing. Mol Immunol 53:302–312PubMedCrossRef
128.
go back to reference Lewin SR et al (2002) Direct evidence for new T cell generation by patients after either T cell-depleted or unmodified allogeneic hematopoietic stem cell transplantations. Blood 100:2235–2242PubMedCrossRef Lewin SR et al (2002) Direct evidence for new T cell generation by patients after either T cell-depleted or unmodified allogeneic hematopoietic stem cell transplantations. Blood 100:2235–2242PubMedCrossRef
129.
go back to reference Weinberg K et al (2001) Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood 97:1458–1466PubMedCrossRef Weinberg K et al (2001) Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood 97:1458–1466PubMedCrossRef
130.
go back to reference Wils EJ et al (2011) Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients. Haematologica 96:1846–1854PubMedPubMedCentralCrossRef Wils EJ et al (2011) Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients. Haematologica 96:1846–1854PubMedPubMedCentralCrossRef
131.
go back to reference van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM (2015) TREC based newborn screening for severe combined immunodeficiency disease: a systematic review. J Clin Immunol 35:416–430PubMedPubMedCentralCrossRef van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM (2015) TREC based newborn screening for severe combined immunodeficiency disease: a systematic review. J Clin Immunol 35:416–430PubMedPubMedCentralCrossRef
132.
go back to reference Chaudhry MS, Velardi E, Malard F, van den Brink MR (2017) Immune reconstitution after allogeneic hematopoietic stem cell transplantation: time to T up the thymus. J Immunol 198:40–46PubMedCrossRef Chaudhry MS, Velardi E, Malard F, van den Brink MR (2017) Immune reconstitution after allogeneic hematopoietic stem cell transplantation: time to T up the thymus. J Immunol 198:40–46PubMedCrossRef
133.
go back to reference Junge S et al (2007) Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. Eur J Immunol 37:3270–3280PubMedCrossRef Junge S et al (2007) Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. Eur J Immunol 37:3270–3280PubMedCrossRef
134.
go back to reference Kohler S, Thiel A (2009) Life after the thymus: CD31+ and CD31- human naive CD4+ T cell subsets. Blood 113:769–774PubMedCrossRef Kohler S, Thiel A (2009) Life after the thymus: CD31+ and CD31- human naive CD4+ T cell subsets. Blood 113:769–774PubMedCrossRef
135.
go back to reference Tanaskovic S, Fernandez S, Price P, Lee S, French MA (2010) CD31 (PECAM-1) is a marker of recent thymic emigrants among CD4+ T cells, but not CD8+ T cells or gammadelta T cells, in HIV patients responding to ART. Immunol Cell Biol 88:321–327PubMedCrossRef Tanaskovic S, Fernandez S, Price P, Lee S, French MA (2010) CD31 (PECAM-1) is a marker of recent thymic emigrants among CD4+ T cells, but not CD8+ T cells or gammadelta T cells, in HIV patients responding to ART. Immunol Cell Biol 88:321–327PubMedCrossRef
136.
go back to reference Elhanati Y, Marcou Q, Mora T, Walczak AM (2016) repgenHMM: a dynamic programming tool to infer the rules of immune receptor generation from sequence data. Bioinformatics 32:1943–1951PubMedPubMedCentralCrossRef Elhanati Y, Marcou Q, Mora T, Walczak AM (2016) repgenHMM: a dynamic programming tool to infer the rules of immune receptor generation from sequence data. Bioinformatics 32:1943–1951PubMedPubMedCentralCrossRef
137.
go back to reference Zarnitsyna VI, Evavold BD, Schoettle LN, Blattman JN, Antia R (2013) Estimating the diversity, completeness, and cross-reactivity of the T cell repertoire. Front Immunol 4:485PubMedPubMedCentralCrossRef Zarnitsyna VI, Evavold BD, Schoettle LN, Blattman JN, Antia R (2013) Estimating the diversity, completeness, and cross-reactivity of the T cell repertoire. Front Immunol 4:485PubMedPubMedCentralCrossRef
139.
142.
go back to reference Laydon DJ, Bangham CR, Asquith B (2015) Estimating T cell repertoire diversity: limitations of classical estimators and a new approach. Philos Trans R Soc Lond Ser B Biol Sci 370:20140291CrossRef Laydon DJ, Bangham CR, Asquith B (2015) Estimating T cell repertoire diversity: limitations of classical estimators and a new approach. Philos Trans R Soc Lond Ser B Biol Sci 370:20140291CrossRef
143.
go back to reference Thomas PG, Handel A, Doherty PC, La Gruta NL (2013) Ecological analysis of antigen-specific CTL repertoires defines the relationship between naive and immune T cell populations. Proc Natl Acad Sci U S A 110:1839–1844PubMedPubMedCentralCrossRef Thomas PG, Handel A, Doherty PC, La Gruta NL (2013) Ecological analysis of antigen-specific CTL repertoires defines the relationship between naive and immune T cell populations. Proc Natl Acad Sci U S A 110:1839–1844PubMedPubMedCentralCrossRef
144.
go back to reference Lewkiewicz S, Chuang YL, Chou T (2019) A mathematical model of the effects of aging on naive T cell populations and diversity. Bull Math Biol 81(7):2783–2817PubMedCrossRef Lewkiewicz S, Chuang YL, Chou T (2019) A mathematical model of the effects of aging on naive T cell populations and diversity. Bull Math Biol 81(7):2783–2817PubMedCrossRef
145.
go back to reference Ciupe SM, Devlin BH, Markert ML, Kepler TB (2013) Quantification of total T cell receptor diversity by flow cytometry and spectratyping. BMC Immunol 14:35PubMedPubMedCentralCrossRef Ciupe SM, Devlin BH, Markert ML, Kepler TB (2013) Quantification of total T cell receptor diversity by flow cytometry and spectratyping. BMC Immunol 14:35PubMedPubMedCentralCrossRef
146.
go back to reference Hou XL, Wang L, Ding YL, Xie Q, Diao HY (2016) Current status and recent advances of next generation sequencing techniques in immunological repertoire. Genes Immun 17:153–164PubMedCrossRef Hou XL, Wang L, Ding YL, Xie Q, Diao HY (2016) Current status and recent advances of next generation sequencing techniques in immunological repertoire. Genes Immun 17:153–164PubMedCrossRef
148.
go back to reference Barennes P et al., (2020) Benchmarking of T cell receptor repertoire profiling methods reveals large systematic biases. Nat Biotechnol Barennes P et al., (2020) Benchmarking of T cell receptor repertoire profiling methods reveals large systematic biases. Nat Biotechnol
149.
151.
go back to reference Warren RL et al (2011) Exhaustive T cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes. Genome Res 21:790–797PubMedPubMedCentralCrossRef Warren RL et al (2011) Exhaustive T cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes. Genome Res 21:790–797PubMedPubMedCentralCrossRef
153.
go back to reference Han A, Glanville J, Hansmann L, Davis MM (2014) Linking T cell receptor sequence to functional phenotype at the single-cell level. Nat Biotechnol 32:684–692PubMedPubMedCentralCrossRef Han A, Glanville J, Hansmann L, Davis MM (2014) Linking T cell receptor sequence to functional phenotype at the single-cell level. Nat Biotechnol 32:684–692PubMedPubMedCentralCrossRef
155.
go back to reference Howie B et al (2015) High-throughput pairing of T cell receptor alpha and beta sequences. Sci Transl Med 7:301ra131PubMedCrossRef Howie B et al (2015) High-throughput pairing of T cell receptor alpha and beta sequences. Sci Transl Med 7:301ra131PubMedCrossRef
156.
go back to reference Wolf K et al (2018) Identifying and tracking low-frequency virus-specific TCR clonotypes using high-throughput sequencing. Cell Rep 25:2369–2378.e2364PubMedPubMedCentralCrossRef Wolf K et al (2018) Identifying and tracking low-frequency virus-specific TCR clonotypes using high-throughput sequencing. Cell Rep 25:2369–2378.e2364PubMedPubMedCentralCrossRef
157.
go back to reference Ahmadzadeh M et al (2019) Tumor-infiltrating human CD4(+) regulatory T cells display a distinct TCR repertoire and exhibit tumor and neoantigen reactivity. Sci Immunol 4:eaao4310PubMedPubMedCentralCrossRef Ahmadzadeh M et al (2019) Tumor-infiltrating human CD4(+) regulatory T cells display a distinct TCR repertoire and exhibit tumor and neoantigen reactivity. Sci Immunol 4:eaao4310PubMedPubMedCentralCrossRef
158.
go back to reference Zoete V, Coukos G (2019) Going beyond the sequences: TCR binding patterns at the service of cancer detection. Cancer Res 79:1299–1301PubMedCrossRef Zoete V, Coukos G (2019) Going beyond the sequences: TCR binding patterns at the service of cancer detection. Cancer Res 79:1299–1301PubMedCrossRef
159.
go back to reference Zheng C et al (2017) Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell 169:1342–1356 e1316PubMedCrossRef Zheng C et al (2017) Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell 169:1342–1356 e1316PubMedCrossRef
161.
go back to reference Smith DJ et al (2004) Mapping the antigenic and genetic evolution of influenza virus. Science 305:371–376PubMedCrossRef Smith DJ et al (2004) Mapping the antigenic and genetic evolution of influenza virus. Science 305:371–376PubMedCrossRef
162.
go back to reference Gil A, Yassai MB, Naumov YN, Selin LK (2015) Narrowing of human influenza A virus-specific T cell receptor α and β repertoires with increasing age. J Virol 89:4102–4116PubMedPubMedCentralCrossRef Gil A, Yassai MB, Naumov YN, Selin LK (2015) Narrowing of human influenza A virus-specific T cell receptor α and β repertoires with increasing age. J Virol 89:4102–4116PubMedPubMedCentralCrossRef
163.
go back to reference Qi Q et al (2016) Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination. Sci Transl Med 8:332ra346CrossRef Qi Q et al (2016) Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination. Sci Transl Med 8:332ra346CrossRef
164.
go back to reference Guo H, Baker SF, Martinez-Sobrido L, Topham DJ (2014) Induction of CD8 T cell heterologous protection by a single dose of single-cycle infectious influenza virus. J Virol 88:12006–12016PubMedPubMedCentralCrossRef Guo H, Baker SF, Martinez-Sobrido L, Topham DJ (2014) Induction of CD8 T cell heterologous protection by a single dose of single-cycle infectious influenza virus. J Virol 88:12006–12016PubMedPubMedCentralCrossRef
165.
166.
go back to reference Waldman AD, Fritz JM, Lenardo MJ (2020) A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol 20(11):651–668PubMedCrossRefPubMedCentral Waldman AD, Fritz JM, Lenardo MJ (2020) A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol 20(11):651–668PubMedCrossRefPubMedCentral
169.
172.
go back to reference Durgeau A, Virk Y, Corgnac S, Mami-Chouaib F (2018) Recent advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy. Front Immunol 9:14PubMedPubMedCentralCrossRef Durgeau A, Virk Y, Corgnac S, Mami-Chouaib F (2018) Recent advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy. Front Immunol 9:14PubMedPubMedCentralCrossRef
173.
go back to reference Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T (2014) Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 14:135–146PubMedCrossRef Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T (2014) Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 14:135–146PubMedCrossRef
174.
go back to reference Zhang H et al (2020) Investigation of antigen-specific T cell receptor clusters in human cancers. Clin Cancer Res 26:1359–1371PubMedCrossRef Zhang H et al (2020) Investigation of antigen-specific T cell receptor clusters in human cancers. Clin Cancer Res 26:1359–1371PubMedCrossRef
175.
go back to reference Aversa I, Malanga D, Fiume G, Palmieri C (2020) Molecular T cell repertoire analysis as source of prognostic and predictive biomarkers for checkpoint blockade immunotherapy. Int J Mol Sci 21:237CrossRef Aversa I, Malanga D, Fiume G, Palmieri C (2020) Molecular T cell repertoire analysis as source of prognostic and predictive biomarkers for checkpoint blockade immunotherapy. Int J Mol Sci 21:237CrossRef
176.
go back to reference Pogorelyy MV et al (2018) Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins. Proc Natl Acad Sci U S A 115:12704–12709PubMedPubMedCentralCrossRef Pogorelyy MV et al (2018) Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins. Proc Natl Acad Sci U S A 115:12704–12709PubMedPubMedCentralCrossRef
177.
go back to reference Hogan SA et al (2019) Peripheral blood TCR repertoire profiling may facilitate patient stratification for immunotherapy against melanoma. Cancer Immunol Res 7:77–85PubMedCrossRef Hogan SA et al (2019) Peripheral blood TCR repertoire profiling may facilitate patient stratification for immunotherapy against melanoma. Cancer Immunol Res 7:77–85PubMedCrossRef
178.
go back to reference Cui JH et al (2018) TCR repertoire as a novel indicator for immune monitoring and prognosis assessment of patients with cervical cancer. Front Immunol 9:2729PubMedPubMedCentralCrossRef Cui JH et al (2018) TCR repertoire as a novel indicator for immune monitoring and prognosis assessment of patients with cervical cancer. Front Immunol 9:2729PubMedPubMedCentralCrossRef
179.
go back to reference Han Y, Li H, Guan Y, Huang J (2016) Immune repertoire: a potential biomarker and therapeutic for hepatocellular carcinoma. Cancer Lett 379:206–212PubMedCrossRef Han Y, Li H, Guan Y, Huang J (2016) Immune repertoire: a potential biomarker and therapeutic for hepatocellular carcinoma. Cancer Lett 379:206–212PubMedCrossRef
181.
go back to reference Arber C et al (2003) Common lymphoid progenitors rapidly engraft and protect against lethal murine cytomegalovirus infection after hematopoietic stem cell transplantation. Blood 102:421–428PubMedCrossRef Arber C et al (2003) Common lymphoid progenitors rapidly engraft and protect against lethal murine cytomegalovirus infection after hematopoietic stem cell transplantation. Blood 102:421–428PubMedCrossRef
182.
go back to reference Zakrzewski JL et al (2006) Adoptive transfer of T cell precursors enhances T cell reconstitution after allogeneic hematopoietic stem cell transplantation. Nat Med 12:1039–1047PubMedCrossRef Zakrzewski JL et al (2006) Adoptive transfer of T cell precursors enhances T cell reconstitution after allogeneic hematopoietic stem cell transplantation. Nat Med 12:1039–1047PubMedCrossRef
183.
go back to reference Awong G et al (2009) Characterization in vitro and engraftment potential in vivo of human progenitor T cells generated from hematopoietic stem cells. Blood 114:972–982PubMedCrossRef Awong G et al (2009) Characterization in vitro and engraftment potential in vivo of human progenitor T cells generated from hematopoietic stem cells. Blood 114:972–982PubMedCrossRef
184.
go back to reference Awong G et al (2013) Human proT cells generated in vitro facilitate hematopoietic stem cell-derived T-lymphopoiesis in vivo and restore thymic architecture. Blood 122:4210–4219PubMedPubMedCentralCrossRef Awong G et al (2013) Human proT cells generated in vitro facilitate hematopoietic stem cell-derived T-lymphopoiesis in vivo and restore thymic architecture. Blood 122:4210–4219PubMedPubMedCentralCrossRef
185.
go back to reference Al-Chami E et al (2016) Interleukin-21 administration to aged mice rejuvenates their peripheral T cell pool by triggering de novo thymopoiesis. Aging Cell 15:349–360PubMedPubMedCentralCrossRef Al-Chami E et al (2016) Interleukin-21 administration to aged mice rejuvenates their peripheral T cell pool by triggering de novo thymopoiesis. Aging Cell 15:349–360PubMedPubMedCentralCrossRef
186.
187.
go back to reference Li L et al (2004) IL-12 inhibits thymic involution by enhancing IL-7- and IL-2-induced thymocyte proliferation. J Immunol 172:2909–2916PubMedCrossRef Li L et al (2004) IL-12 inhibits thymic involution by enhancing IL-7- and IL-2-induced thymocyte proliferation. J Immunol 172:2909–2916PubMedCrossRef
188.
go back to reference Chen T et al (2007) IL-12 facilitates both the recovery of endogenous hematopoiesis and the engraftment of stem cells after ionizing radiation. Exp Hematol 35:203–213PubMedCrossRef Chen T et al (2007) IL-12 facilitates both the recovery of endogenous hematopoiesis and the engraftment of stem cells after ionizing radiation. Exp Hematol 35:203–213PubMedCrossRef
189.
go back to reference Campinoti S et al (2020) Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds. Nat Commun 11:6372PubMedPubMedCentralCrossRef Campinoti S et al (2020) Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds. Nat Commun 11:6372PubMedPubMedCentralCrossRef
190.
go back to reference Bosticardo M et al (2020) Artificial thymic organoids represent a reliable tool to study T cell differentiation in patients with severe T cell lymphopenia. Blood Adv 4:2611–2616PubMedPubMedCentralCrossRef Bosticardo M et al (2020) Artificial thymic organoids represent a reliable tool to study T cell differentiation in patients with severe T cell lymphopenia. Blood Adv 4:2611–2616PubMedPubMedCentralCrossRef
191.
go back to reference Rosenberg SA et al (2006) IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother 29:313–319PubMedPubMedCentralCrossRef Rosenberg SA et al (2006) IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother 29:313–319PubMedPubMedCentralCrossRef
192.
go back to reference Sportes C et al (2008) Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med 205:1701–1714PubMedPubMedCentralCrossRef Sportes C et al (2008) Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med 205:1701–1714PubMedPubMedCentralCrossRef
193.
go back to reference Levy Y et al (2009) Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest 119:997–1007PubMedPubMedCentral Levy Y et al (2009) Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest 119:997–1007PubMedPubMedCentral
194.
go back to reference Sportes C et al (2010) Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. Clin Cancer Res 16:727–735PubMedPubMedCentralCrossRef Sportes C et al (2010) Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. Clin Cancer Res 16:727–735PubMedPubMedCentralCrossRef
195.
go back to reference Levy Y et al (2012) Effects of recombinant human interleukin 7 on T cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis 55:291–300PubMedPubMedCentralCrossRef Levy Y et al (2012) Effects of recombinant human interleukin 7 on T cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis 55:291–300PubMedPubMedCentralCrossRef
196.
go back to reference Perales MA et al (2012) Recombinant human interleukin-7 (CYT107) promotes T cell recovery after allogeneic stem cell transplantation. Blood 120:4882–4891PubMedPubMedCentralCrossRef Perales MA et al (2012) Recombinant human interleukin-7 (CYT107) promotes T cell recovery after allogeneic stem cell transplantation. Blood 120:4882–4891PubMedPubMedCentralCrossRef
197.
go back to reference Min D et al (2007) Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood 109:2529–2537PubMedPubMedCentralCrossRef Min D et al (2007) Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood 109:2529–2537PubMedPubMedCentralCrossRef
198.
199.
go back to reference Goldberg JD et al (2013) Palifermin is efficacious in recipients of TBI-based but not chemotherapy-based allogeneic hematopoietic stem cell transplants. Bone Marrow Transplant 48:99–104PubMedCrossRef Goldberg JD et al (2013) Palifermin is efficacious in recipients of TBI-based but not chemotherapy-based allogeneic hematopoietic stem cell transplants. Bone Marrow Transplant 48:99–104PubMedCrossRef
200.
go back to reference Pan B et al (2019) Interleukin-22 accelerates thymus regeneration via Stat3/Mcl-1 and decreases chronic graft-versus-host disease in mice after allotransplants. Biol Blood Marrow Transplant 25:1911–1919PubMedCrossRef Pan B et al (2019) Interleukin-22 accelerates thymus regeneration via Stat3/Mcl-1 and decreases chronic graft-versus-host disease in mice after allotransplants. Biol Blood Marrow Transplant 25:1911–1919PubMedCrossRef
201.
go back to reference Perruccio K et al (2010) Thymosin alpha1 to harness immunity to pathogens after haploidentical hematopoietic transplantation. Ann N Y Acad Sci 1194:153–161PubMedCrossRef Perruccio K et al (2010) Thymosin alpha1 to harness immunity to pathogens after haploidentical hematopoietic transplantation. Ann N Y Acad Sci 1194:153–161PubMedCrossRef
202.
go back to reference Liu Y et al (2020) Thymosin alpha 1 reduces the mortality of severe coronavirus disease 2019 by restoration of lymphocytopenia and reversion of exhausted T cells. Clin Infect Dis 71:2150–2157PubMedCrossRef Liu Y et al (2020) Thymosin alpha 1 reduces the mortality of severe coronavirus disease 2019 by restoration of lymphocytopenia and reversion of exhausted T cells. Clin Infect Dis 71:2150–2157PubMedCrossRef
203.
go back to reference Sutherland JS et al (2008) Enhanced immune system regeneration in humans following allogeneic or autologous hemopoietic stem cell transplantation by temporary sex steroid blockade. Clin Cancer Res 14:1138–1149PubMedCrossRef Sutherland JS et al (2008) Enhanced immune system regeneration in humans following allogeneic or autologous hemopoietic stem cell transplantation by temporary sex steroid blockade. Clin Cancer Res 14:1138–1149PubMedCrossRef
206.
go back to reference Kang J, Der SD (2004) Cytokine functions in the formative stages of a lymphocyte’s life. Curr Opin Immunol 16:180–190PubMedCrossRef Kang J, Der SD (2004) Cytokine functions in the formative stages of a lymphocyte’s life. Curr Opin Immunol 16:180–190PubMedCrossRef
207.
208.
go back to reference Fry TJ et al (2003) IL-7 therapy dramatically alters peripheral T cell homeostasis in normal and SIV-infected nonhuman primates. Blood 101:2294–2299PubMedCrossRef Fry TJ et al (2003) IL-7 therapy dramatically alters peripheral T cell homeostasis in normal and SIV-infected nonhuman primates. Blood 101:2294–2299PubMedCrossRef
209.
go back to reference Chu YW et al (2004) Exogenous IL-7 increases recent thymic emigrants in peripheral lymphoid tissue without enhanced thymic function. Blood 104:1110–1119PubMedCrossRef Chu YW et al (2004) Exogenous IL-7 increases recent thymic emigrants in peripheral lymphoid tissue without enhanced thymic function. Blood 104:1110–1119PubMedCrossRef
210.
go back to reference Alpdogan O et al (2003) IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation. J Clin Invest 112:1095–1107PubMedPubMedCentralCrossRef Alpdogan O et al (2003) IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation. J Clin Invest 112:1095–1107PubMedPubMedCentralCrossRef
211.
go back to reference Andrew D, Aspinall R (2001) Il-7 and not stem cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice. J Immunol 166:1524–1530PubMedCrossRef Andrew D, Aspinall R (2001) Il-7 and not stem cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice. J Immunol 166:1524–1530PubMedCrossRef
212.
go back to reference Sportès C et al (2008) Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med 205:1701–1714PubMedPubMedCentralCrossRef Sportès C et al (2008) Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med 205:1701–1714PubMedPubMedCentralCrossRef
213.
go back to reference Spielberger R et al (2004) Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 351:2590–2598PubMedCrossRef Spielberger R et al (2004) Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 351:2590–2598PubMedCrossRef
214.
go back to reference Seggewiss R et al (2007) Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood 110:441–449PubMedPubMedCentralCrossRef Seggewiss R et al (2007) Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood 110:441–449PubMedPubMedCentralCrossRef
215.
go back to reference Shang L et al (2021) Dynamic of plasma IL-22 level is an indicator of thymic output after allogeneic hematopoietic cell transplantation. Life Sci 265:118849PubMedCrossRef Shang L et al (2021) Dynamic of plasma IL-22 level is an indicator of thymic output after allogeneic hematopoietic cell transplantation. Life Sci 265:118849PubMedCrossRef
216.
go back to reference Bando JK et al (2018) The tumor necrosis factor superfamily member RANKL suppresses effector cytokine production in group 3 innate lymphoid cells. Immunity 48:1208–1219PubMedPubMedCentralCrossRef Bando JK et al (2018) The tumor necrosis factor superfamily member RANKL suppresses effector cytokine production in group 3 innate lymphoid cells. Immunity 48:1208–1219PubMedPubMedCentralCrossRef
218.
go back to reference Sutherland JS et al (2005) Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol 175:2741–2753PubMedCrossRef Sutherland JS et al (2005) Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol 175:2741–2753PubMedCrossRef
219.
go back to reference Goldberg GL et al (2009) Luteinizing hormone-releasing hormone enhances T cell recovery following allogeneic bone marrow transplantation. J Immunol 182:5846–5854PubMedCrossRef Goldberg GL et al (2009) Luteinizing hormone-releasing hormone enhances T cell recovery following allogeneic bone marrow transplantation. J Immunol 182:5846–5854PubMedCrossRef
220.
go back to reference Dudakov JA, Goldberg GL, Reiseger JJ, Chidgey AP, Boyd RL (2009) Withdrawal of sex steroids reverses age- and chemotherapy-related defects in bone marrow lymphopoiesis. J Immunol 182:6247–6260PubMedCrossRef Dudakov JA, Goldberg GL, Reiseger JJ, Chidgey AP, Boyd RL (2009) Withdrawal of sex steroids reverses age- and chemotherapy-related defects in bone marrow lymphopoiesis. J Immunol 182:6247–6260PubMedCrossRef
221.
go back to reference Khong DM et al (2015) Enhanced hematopoietic stem cell function mediates immune regeneration following sex steroid blockade. Stem Cell Rep 4:445–458CrossRef Khong DM et al (2015) Enhanced hematopoietic stem cell function mediates immune regeneration following sex steroid blockade. Stem Cell Rep 4:445–458CrossRef
222.
go back to reference Krueger A, Willenzon S, Lyszkiewicz M, Kremmer E, Forster R (2010) CC chemokine receptor 7 and 9 double-deficient hematopoietic progenitors are severely impaired in seeding the adult thymus. Blood 115:1906–1912PubMedCrossRef Krueger A, Willenzon S, Lyszkiewicz M, Kremmer E, Forster R (2010) CC chemokine receptor 7 and 9 double-deficient hematopoietic progenitors are severely impaired in seeding the adult thymus. Blood 115:1906–1912PubMedCrossRef
224.
go back to reference Goldberg GL et al (2005) Sex steroid ablation enhances lymphoid recovery following autologous hematopoietic stem cell transplantation. Transplantation 80:1604–1613PubMedCrossRef Goldberg GL et al (2005) Sex steroid ablation enhances lymphoid recovery following autologous hematopoietic stem cell transplantation. Transplantation 80:1604–1613PubMedCrossRef
225.
go back to reference Goldberg GL et al (2007) Enhanced immune reconstitution by sex steroid ablation following allogeneic hemopoietic stem cell transplantation. J Immunol 178:7473–7484PubMedCrossRef Goldberg GL et al (2007) Enhanced immune reconstitution by sex steroid ablation following allogeneic hemopoietic stem cell transplantation. J Immunol 178:7473–7484PubMedCrossRef
226.
go back to reference Taub DD, Murphy WJ, Longo DL (2010) Rejuvenation of the aging thymus: growth hormone-mediated and ghrelin-mediated signaling pathways. Curr Opin Pharmacol 10:408–424PubMedPubMedCentralCrossRef Taub DD, Murphy WJ, Longo DL (2010) Rejuvenation of the aging thymus: growth hormone-mediated and ghrelin-mediated signaling pathways. Curr Opin Pharmacol 10:408–424PubMedPubMedCentralCrossRef
228.
229.
go back to reference Carlo-Stella C et al (2004) Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone. Exp Hematol 32:171–178PubMedCrossRef Carlo-Stella C et al (2004) Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone. Exp Hematol 32:171–178PubMedCrossRef
230.
go back to reference Herasimtschuk AA, Westrop SJ, Moyle GJ, Downey JS, Imami N (2008) Effects of recombinant human growth hormone on HIV-1-specific T cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up. J Immune Based Ther Vaccines 6:7PubMedPubMedCentralCrossRef Herasimtschuk AA, Westrop SJ, Moyle GJ, Downey JS, Imami N (2008) Effects of recombinant human growth hormone on HIV-1-specific T cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up. J Immune Based Ther Vaccines 6:7PubMedPubMedCentralCrossRef
231.
go back to reference Napolitano LA et al (2008) Growth hormone enhances thymic function in HIV-1-infected adults. J Clin Invest 118:1085–1098PubMedPubMedCentral Napolitano LA et al (2008) Growth hormone enhances thymic function in HIV-1-infected adults. J Clin Invest 118:1085–1098PubMedPubMedCentral
232.
go back to reference Napolitano LA et al (2002) Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone. AIDS 16:1103–1111PubMedCrossRef Napolitano LA et al (2002) Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone. AIDS 16:1103–1111PubMedCrossRef
233.
go back to reference Plana M et al (2011) The reconstitution of the thymus in immunosuppressed individuals restores CD4-specific cellular and humoral immune responses. Immunology 133:318–328PubMedPubMedCentralCrossRef Plana M et al (2011) The reconstitution of the thymus in immunosuppressed individuals restores CD4-specific cellular and humoral immune responses. Immunology 133:318–328PubMedPubMedCentralCrossRef
234.
235.
go back to reference Seet CS et al (2017) Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids. Nat Methods advance online publication 14:521–530PubMedPubMedCentralCrossRef Seet CS et al (2017) Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids. Nat Methods advance online publication 14:521–530PubMedPubMedCentralCrossRef
236.
go back to reference Shukla S et al (2017) Progenitor T cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1. Nat Methods 14:531PubMedCrossRef Shukla S et al (2017) Progenitor T cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1. Nat Methods 14:531PubMedCrossRef
237.
238.
go back to reference Chidgey AP, Seach N, Dudakov J, Hammett MV, Boyd RL (2008) Strategies for reconstituting and boosting T cell-based immunity following haematopoietic stem cell transplantation: pre-clinical and clinical approaches. Semin Immunopathol 30:457–477PubMedCrossRef Chidgey AP, Seach N, Dudakov J, Hammett MV, Boyd RL (2008) Strategies for reconstituting and boosting T cell-based immunity following haematopoietic stem cell transplantation: pre-clinical and clinical approaches. Semin Immunopathol 30:457–477PubMedCrossRef
239.
go back to reference Seach N, Layton D, Lim J, Chidgey A, Boyd R (2007) Thymic generation and regeneration: a new paradigm for establishing clinical tolerance of stem cell-based therapies. Curr Opin Biotechnol 18:441–447PubMedCrossRef Seach N, Layton D, Lim J, Chidgey A, Boyd R (2007) Thymic generation and regeneration: a new paradigm for establishing clinical tolerance of stem cell-based therapies. Curr Opin Biotechnol 18:441–447PubMedCrossRef
240.
241.
go back to reference Fan Y et al (2015) Bioengineering thymus organoids to restore thymic function and induce donor-specific immune tolerance to allografts. Mol Ther 23:1262–1277PubMedPubMedCentralCrossRef Fan Y et al (2015) Bioengineering thymus organoids to restore thymic function and induce donor-specific immune tolerance to allografts. Mol Ther 23:1262–1277PubMedPubMedCentralCrossRef
242.
go back to reference Tajima A, Pradhan I, Geng X, Trucco M, Fan Y (2019) Construction of thymus organoids from decellularized thymus scaffolds. Methods Mol Biol (Clifton, NJ) 1576:33–42CrossRef Tajima A, Pradhan I, Geng X, Trucco M, Fan Y (2019) Construction of thymus organoids from decellularized thymus scaffolds. Methods Mol Biol (Clifton, NJ) 1576:33–42CrossRef
243.
go back to reference Gill J, Malin M, Hollander GA, Boyd R (2002) Generation of a complete thymic microenvironment by MTS24(+) thymic epithelial cells. Nat Immunol 3:635–642PubMedCrossRef Gill J, Malin M, Hollander GA, Boyd R (2002) Generation of a complete thymic microenvironment by MTS24(+) thymic epithelial cells. Nat Immunol 3:635–642PubMedCrossRef
244.
go back to reference Bennett AR et al (2002) Identification and characterization of thymic epithelial progenitor cells. Immunity 16:803–814PubMedCrossRef Bennett AR et al (2002) Identification and characterization of thymic epithelial progenitor cells. Immunity 16:803–814PubMedCrossRef
245.
go back to reference Depreter MG et al (2008) Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells. Proc Natl Acad Sci U S A 105:961–966PubMedPubMedCentralCrossRef Depreter MG et al (2008) Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells. Proc Natl Acad Sci U S A 105:961–966PubMedPubMedCentralCrossRef
246.
go back to reference Rossi SW et al (2007) Redefining epithelial progenitor potential in the developing thymus. Eur J Immunol 37:2411–2418PubMedCrossRef Rossi SW et al (2007) Redefining epithelial progenitor potential in the developing thymus. Eur J Immunol 37:2411–2418PubMedCrossRef
247.
go back to reference Lai L et al (2011) Mouse embryonic stem cell-derived thymic epithelial cell progenitors enhance T cell reconstitution after allogeneic bone marrow transplantation. Blood 118:3410–3418PubMedCrossRef Lai L et al (2011) Mouse embryonic stem cell-derived thymic epithelial cell progenitors enhance T cell reconstitution after allogeneic bone marrow transplantation. Blood 118:3410–3418PubMedCrossRef
248.
go back to reference Lai L, Jin J (2009) Generation of thymic epithelial cell progenitors by mouse embryonic stem cells. Stem Cells 27:3012–3020PubMedCrossRef Lai L, Jin J (2009) Generation of thymic epithelial cell progenitors by mouse embryonic stem cells. Stem Cells 27:3012–3020PubMedCrossRef
249.
go back to reference Kim M-J, Miller CM, Shadrach JL, Wagers AJ, Serwold T (2015) Young, proliferative thymic epithelial cells engraft and function in aging thymuses. J Immunol 194:4784–4795PubMedCrossRef Kim M-J, Miller CM, Shadrach JL, Wagers AJ, Serwold T (2015) Young, proliferative thymic epithelial cells engraft and function in aging thymuses. J Immunol 194:4784–4795PubMedCrossRef
251.
go back to reference Wong K et al (2014) Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus. Cell Rep 8:1198–1209PubMedCrossRef Wong K et al (2014) Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus. Cell Rep 8:1198–1209PubMedCrossRef
252.
go back to reference Bleul CC et al (2006) Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 441:992–996PubMedCrossRef Bleul CC et al (2006) Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 441:992–996PubMedCrossRef
254.
go back to reference Chhatta AR et al (2019) De novo generation of a functional human thymus from induced pluripotent stem cells. J Allergy Clin Immunol 144:1416–1419.e1417PubMedCrossRef Chhatta AR et al (2019) De novo generation of a functional human thymus from induced pluripotent stem cells. J Allergy Clin Immunol 144:1416–1419.e1417PubMedCrossRef
Metadata
Title
Dynamics of thymus function and T cell receptor repertoire breadth in health and disease
Authors
David Granadier
Lorenzo Iovino
Sinéad Kinsella
Jarrod A. Dudakov
Publication date
01-02-2021
Publisher
Springer Berlin Heidelberg
Published in
Seminars in Immunopathology / Issue 1/2021
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-021-00840-5

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