Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Research

Aberrant T cell responses in the bone marrow microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation

Authors: Yuan Kong, Yu-Tong Wang, Xie-Na Cao, Yang Song, Yu-Hong Chen, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang

Published in: Journal of Translational Medicine | Issue 1/2017

Login to get access

Abstract

Background

Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, whether abnormalities of T cell subsets in the bone marrow (BM) immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains unclear.

Methods

This prospective nested case–control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD). Th17, Tc17, Th1, Tc1, Th2, Tc2 cells, Tregs and their subsets were analyzed by flow cytometry.

Results

A significantly higher proportion of stimulated CD4+ and CD8+ T cells that produced IL-17 (Th17 and Tc17) was found in the BM of PGF patients than in the BM of GGF patients and HD, whereas the percentages of Tregs in PGF patients were comparable to those in GGF patients and HD, resulting in a dramatically elevated ratio of Th17 cells/Tregs in the BM of PGF patients relative to those in GGF patients. Moreover, both CD4+ and CD8+ T cells were polarized towards a type 1 immune response in the BM of PGF patients.

Conclusions

The present study revealed that aberrant T cell responses in the BM immune microenvironment may be involved in the pathogenesis of PGF after allo-HSCT. These findings will facilitate the optimization of immune regulation strategies and improve the outcome of PGF patients post-allotransplant.
Appendix
Available only for authorised users
Literature
1.
Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A, et al. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica. 2006;91:935–40.PubMed
2.
Olsson RF, Logan BR, Chaudhury S, Zhu X, Akpek G, Bolwell BJ, Bredeson CN, Dvorak CC, Gupta V, Ho VT, et al. Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies. Leukemia. 2015;29:1754–62.CrossRefPubMedPubMedCentral
3.
Reisner Y, Hagin D, Martelli MF. Haploidentical hematopoietic transplantation: current status and future perspectives. Blood. 2011;118:6006–17.CrossRefPubMed
4.
5.
6.
7.
Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–6.CrossRefPubMed
8.
9.
Kong Y, Song Y, Hu Y, Shi MM, Wang YT, Wang Y, Zhang XH, Xu LP, Liu KY, Deng HK, Huang XJ. Increased reactive oxygen species and exhaustion of quiescent CD34-positive bone marrow cells may contribute to poor graft function after allotransplants. Oncotarget. 2016;7:30892–906.PubMedPubMedCentral
10.
Kong Y, Chang YJ, Wang YZ, Chen YH, Han W, Wang Y, Sun YQ, Yan CH, Wang FR, Liu YR, et al. Association of an impaired bone marrow microenvironment with secondary poor graft function after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19:1465–73.CrossRefPubMed
11.
Kong Y, Wang YT, Hu Y, Han W, Chang YJ, Zhang XH, Jiang ZF, Huang XJ. The bone marrow microenvironment is similarly impaired in allogeneic hematopoietic stem cell transplantation patients with early and late poor graft function. Bone Marrow Transplant. 2016;51:249–55.CrossRefPubMed
12.
Shi MM, Kong Y, Song Y, Sun YQ, Wang Y, Zhang XH, Xu LP, Liu KY, Huang XJ. Atorvastatin enhances endothelial cell function in posttransplant poor graft function. Blood. 2016;128:2988–99.CrossRefPubMed
13.
14.
Riether C, Schurch CM, Ochsenbein AF. Regulation of hematopoietic and leukemic stem cells by the immune system. Cell Death Differ. 2015;22:187–98.CrossRefPubMed
15.
Shono Y, Ueha S, Wang Y, Abe J, Kurachi M, Matsuno Y, Sugiyama T, Nagasawa T, Imamura M, Matsushima K. Bone marrow graft-versus-host disease: early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation. Blood. 2010;115:5401–11.CrossRefPubMed
16.
Yao Y, Song X, Cheng H, Tang G, Hu X, Zhou H, Wang J. Dysfunction of bone marrow vascular niche in acute graft-versus-host disease after MHC-haploidentical bone marrow transplantation. PLoS ONE. 2014;9:e104607.CrossRefPubMedPubMedCentral
17.
Wang YT, Kong Y, Song Y, Han W, Zhang YY, Zhang XH, Chang YJ, Jiang ZF, Huang XJ. Increased type 1 immune response in the bone marrow immune microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2016;22:1376–82.CrossRefPubMed
18.
Zuniga LA, Jain R, Haines C, Cua DJ. Th17 cell development: from the cradle to the grave. Immunol Rev. 2013;252:78–88.CrossRefPubMed
19.
Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N, Becher B, Prat A. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med. 2007;13:1173–5.CrossRefPubMedPubMedCentral
20.
Singh RP, Hasan S, Sharma S, Nagra S, Yamaguchi DT, Wong DT, Hahn BH, Hossain A. Th17 cells in inflammation and autoimmunity. Autoimmun Rev. 2014;13:1174–81.CrossRefPubMed
21.
Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity. 2005;22:329–41.CrossRefPubMed
22.
Gagliani N, Vesely MCA, Iseppon A, Brockmann L, Xu H, Palm NW, de Zoete MR, Licona-Limon P, Paiva RS, Ching T, et al. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature. 2015;523:221–5.CrossRefPubMedPubMedCentral
23.
Klatka M, Grywalska E, Partyka M, Charytanowicz M, Kiszczak-Bochynska E, Rolinski J. Th17 and Treg cells in adolescents with Graves’ disease. impact of treatment with methimazole on these cell subsets. Autoimmunity. 2014;47:201–11.CrossRefPubMed
24.
Ratajczak P, Janin A, de Latour RP, Leboeuf C, Desveaux A, Keyvanfar K, Robin M, Clave E, Douay C, Quinquenel A, et al. Th17/Treg ratio in human graft-versus-host disease. Blood. 2010;116:1165–71.CrossRefPubMedPubMedCentral
25.
Song Y, Wang YT, Huang XJ, Kong Y. Abnormalities of the bone marrow immune microenvironment in patients with immune thrombocytopenia. Ann Hematol. 2016;95:959–65.CrossRefPubMed
26.
Zhao XY, Xu LL, Lu SY, Huang XJ. IL-17-producing T cells contribute to acute graft-versus-host disease in patients undergoing unmanipulated blood and marrow transplantation. Eur J Immunol. 2011;41:514–26.CrossRefPubMed
27.
Fujisaki J, Wu J, Carlson AL, Silberstein L, Putheti P, Larocca R, Gao W, Saito TI, Celso CL, Tsuyuzaki H, et al. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature. 2011;474:216–9.CrossRefPubMedPubMedCentral
28.
Wacholder S, Silverman DT, McLaughlin JK, Mandel JS. Selection of controls in case–control studies. III. Design options. Am J Epidemiol. 1992;135:1042–50.CrossRefPubMed
29.
Chang YJ, Xu LP, Wang Y, Zhang XH, Chen H, Chen YH, Wang FR, Han W, Sun YQ, Yan CH, et al. Controlled, randomized, open-label trial of risk-stratified corticosteroid prevention of acute graft-versus-host disease after haploidentical transplantation. J Clin Oncol. 2016;34:1855–63.CrossRefPubMed
30.
Huang XJ, Zhu HH, Chang YJ, Xu LP, Liu DH, Zhang XH, Jiang B, Jiang Q, Jiang H, Chen YH, et al. The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission. Blood. 2012;119:5584–90.CrossRefPubMed
31.
Wang Y, Chang YJ, Xu LP, Liu KY, Liu DH, Zhang XH, Chen H, Han W, Chen YH, Wang FR, et al. Who is the best donor for a related HLA haplotype-mismatched transplant? Blood. 2014;124:843–50.CrossRefPubMed
32.
Wang Y, Wu DP, Liu QF, Qin YZ, Wang JB, Xu LP, Liu YR, Zhu HH, Chen J, Dai M, Huang XJ. In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification. Blood. 2014;124:1880–6.CrossRefPubMed
33.
Xu LP, Huang XJ, Guo NL, Ren HY, Zhang YC, Lu DP. Detection of cytomegalovirus infection by polymerase chain reaction in hematopoietic stem cell transplantation recipients. Zhonghua Xue Ye Xue Za Zhi. 2003;24:407–9.PubMed
34.
Kong Y, Hu Y, Zhang XH, Wang YZ, Mo XD, Zhang YY, Wang Y, Han W, Xu LP, Chang YJ, Huang XJ. Association between an impaired bone marrow vascular microenvironment and prolonged isolated thrombocytopenia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20:1190–7.CrossRefPubMed
35.
Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the human immunology project. Nat Rev Immunol. 2012;12:191–200.PubMedPubMedCentral
36.
Dong S, Maiella S, Xhaard A, Pang Y, Wenandy L, Larghero J, Becavin C, Benecke A, Bianchi E, Socie G, Rogge L. Multiparameter single-cell profiling of human CD4+ FOXP3+ regulatory T-cell populations in homeostatic conditions and during graft-versus-host disease. Blood. 2013;122:1802–12.CrossRefPubMed
37.
Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, Parizot C, Taflin C, Heike T, Valeyre D, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity. 2009;30:899–911.CrossRefPubMed
38.
Giannakoulas NC, Karakantza M, Theodorou GL, Pagoni M, Galanopoulos A, Kakagianni T, Kouraklis-Symeonidis A, Matsouka P, Maniatis A, Zoumbos NC. Clinical relevance of balance between type 1 and type 2 immune responses of lymphocyte subpopulations in aplastic anaemia patients. Br J Haematol. 2004;124:97–105.CrossRefPubMed
39.
Sloand E, Kim S, Maciejewski JP, Tisdale J, Follmann D, Young NS. Intracellular interferon-gamma in circulating and marrow T cells detected by flow cytometry and the response to immunosuppressive therapy in patients with aplastic anemia. Blood. 2002;100:1185–91.CrossRefPubMed
40.
Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, Han ZC. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica. 2005;90:914–23.PubMed
41.
de Latour RP, Visconte V, Takaku T, Wu C, Erie AJ, Sarcon AK, Desierto MJ, Scheinberg P, Keyvanfar K, Nunez O, et al. Th17 immune responses contribute to the pathophysiology of aplastic anemia. Blood. 2010;116:4175–84.CrossRefPubMedPubMedCentral
42.
Tao B, Ruan G, Wang D, Li Y, Wang Z, Yin G. Imbalance of peripheral Th17 and regulatory T Cells in children with allergic Rhinitis AND bronchial asthma. Iran J Allergy Asthma Immunol. 2015;14:273–9.PubMed
43.
Zheng Q, Yang T, Fang L, Liu L, Liu H, Zhao H, Zhao Y, Guo H, Fan Y, Wang L. Effects of Bu Shen Yi Sui Capsule on Th17/Treg cytokines in C57BL/6 mice with experimental autoimmune encephalomyelitis. BMC Complement Altern Med. 2015;15:60.CrossRefPubMedPubMedCentral
44.
Wang R, Solt LA. Metabolism of murine TH 17 cells: impact on cell fate and function. Eur J Immunol. 2016;46:807–16.CrossRefPubMed
45.
Shi J, Ge M, Lu S, Li X, Shao Y, Huang J, Huang Z, Zhang J, Nie N, Zheng Y. Intrinsic impairment of CD4(+)CD25(+) regulatory T cells in acquired aplastic anemia. Blood. 2012;120:1624–32.CrossRefPubMed
46.
Solomou EE, Rezvani K, Mielke S, Malide D, Keyvanfar K, Visconte V, Kajigaya S, Barrett AJ, Young NS. Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia. Blood. 2007;110:1603–6.CrossRefPubMedPubMedCentral
Metadata
Title
Aberrant T cell responses in the bone marrow microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation
Authors
Yuan Kong
Yu-Tong Wang
Xie-Na Cao
Yang Song
Yu-Hong Chen
Yu-Qian Sun
Yu Wang
Xiao-Hui Zhang
Lan-Ping Xu
Xiao-Jun Huang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1159-y

Other articles of this Issue 1/2017

Journal of Translational Medicine 1/2017 Go to the issue

Research

Xenon in the treatment of panic disorder: an open label study

Research

Identification of miRNA-mRNA crosstalk in CD4+ T cells during HIV-1 infection by integrating transcriptome analyses

Research

The impact of antiretroviral therapy on iron homeostasis and inflammation markers in HIV-infected patients with mild anemia

Research

Erythrocyte depletion from bone marrow: performance evaluation after 50 clinical-scale depletions with Spectra Optia BMC

Research

Gimatecan exerts potent antitumor activity against gastric cancer in vitro and in vivo via AKT and MAPK signaling pathways

Review

p53: key conductor of all anti-acne therapies
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits