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Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 2/2014

01-10-2014

Alteration of Regulatory T Cells in Type 1 Diabetes Mellitus: A Comprehensive Review

Authors: Tingting Tan, Yufei Xiang, Christopher Chang, Zhiguang Zhou

Published in: Clinical Reviews in Allergy & Immunology | Issue 2/2014

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Abstract

Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease characterized by the destruction of pancreatic β cells. Numerous studies have demonstrated the key role of CD4+CD25+FoxP3+ regulatory T cells (Tregs) in the development of T1DM. However, the changes in Treg expression and function as well as the regulation of these activities are not clearly elucidated. Most studies on the role of Tregs in T1DM were performed on peripheral blood rather than pancreas or pancreatic lymph nodes. Tissue-based studies are more difficult to perform, and there is a lack of histological data to support the role of Tregs in T1DM. In spite of this, strategies to increase Treg cell number and/or function have been viewed as potential therapeutic approaches in treating T1DM, and several clinical trials using these strategies have already emerged. Notably, many trials fail to demonstrate clinical response even when Treg treatment successfully boosts Tregs. In view of this, whether a failure of Tregs does exist and contribute to the development of T1DM and whether more Tregs would be clinically beneficial to patients should be carefully taken into consideration before applying Tregs as treatments in T1DM.
Literature
1.
van Belle TL, Coppieters KT, von Herrath MG (2011) Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 91:79–118PubMedCrossRef
2.
Eisenbarth GS (1986) Type I, diabetes mellitus. A chronic autoimmune disease. N Engl J Med 314:1360–1368PubMedCrossRef
3.
Chen W, Xie A, Chan L (2013) Mechanistic basis of immunotherapies for type 1 diabetes mellitus. Transl Res : J Lab Clin Med 161:217–229CrossRef
4.
Askenasy EM, Askenasy N (2013) Is autoimmune diabetes caused by aberrant immune activity or defective suppression of physiological self-reactivity? Autoimmun Rev 12:633–637PubMedCrossRef
5.
Gagnerault MC, Luan JJ, Lotton C, Lepault F (2002) Pancreatic lymph nodes are required for priming of beta cell reactive T cells in NOD mice. J Exp Med 196:369–377PubMedPubMedCentralCrossRef
6.
Xiao J, Liu C, Li G, Peng S, Hu J, Qu L et al (2013) PDCD5 negatively regulates autoimmunity by upregulating FOXP3(+) regulatory T cells and suppressing Th17 and Th1 responses. J Autoimmun 47:34–44PubMedCrossRef
7.
8.
9.
Longhi MS, Ma Y, Grant CR, Samyn M, Gordon P, Mieli-Vergani G et al (2013) T-regs in autoimmune hepatitis-systemic lupus erythematosus/mixed connective tissue disease overlap syndrome are functionally defective and display a Th1 cytokine profile. J Autoimmun 41:146–151PubMedCrossRef
10.
Peterson RA (2012) Regulatory T-cells: diverse phenotypes integral to immune homeostasis and suppression. Toxicol Pathol 40:186–204PubMedCrossRef
11.
Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10:490–500PubMedCrossRef
12.
Battaglia M, Roncarolo MG (2011) Immune intervention with T regulatory cells: past lessons and future perspectives for type 1 diabetes. Semin Immunol 23:182–194PubMedCrossRef
13.
14.
Venigalla RK, Guttikonda PJ, Eckstein V, Ho AD, Sertel S, Lorenz HM et al (2012) Identification of a human Th1-like IFNgamma-secreting Treg subtype deriving from effector T cells. J Autoimmun 39:377–387PubMedCrossRef
15.
Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4:330–336PubMedCrossRef
16.
Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science (New York, NY) 299:1057–1061CrossRef
17.
You S, Thieblemont N, Alyanakian MA, Bach JF, Chatenoud L (2006) Transforming growth factor-beta and T-cell-mediated immunoregulation in the control of autoimmune diabetes. Immunol Rev 212:185–202PubMedCrossRef
18.
Gershon RK, Kondo K (1970) Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 18:723–737PubMedPubMedCentral
19.
Benacerraf B, Kapp JA, Debre P, Pierce CW, de la Croix F (1975) The stimulation of specific suppressor T cells in genetic non-responder mice by linear random copolymers of L-amino acids. Transplant Rev 26:21–38PubMed
20.
Bach JF, Boitard C, Yasunami R, Dardenne M (1990) Control of diabetes in NOD mice by suppressor cells. J Autoimmun 3(Suppl 1):97–100PubMedCrossRef
21.
Boitard C, Yasunami R, Dardenne M, Bach JF (1989) T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD mice. J Exp Med 169:1669–1680PubMedCrossRef
22.
Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (2011) Pillars article: immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995. J Immunol (Baltimore, Md: 1950), 186:3808–3821
23.
Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N et al (2000) Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 192:303–310PubMedPubMedCentralCrossRef
24.
Thornton AM, Shevach EM (1998) CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 188:287–296PubMedPubMedCentralCrossRef
25.
Thornton AM, Shevach EM (2000) Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J Immunol (Baltimore, Md: 1950) 164:183–190CrossRef
26.
Piccirillo CA, Tritt M, Sgouroudis E, Albanese A, Pyzik M, Hay V (2005) Control of type 1 autoimmune diabetes by naturally occurring CD4+CD25+ regulatory T lymphocytes in neonatal NOD mice. Ann N Y Acad Sci 1051:72–87PubMedCrossRef
27.
Khattri R, Cox T, Yasayko SA, Ramsdell F (2003) An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 4:337–342PubMedCrossRef
28.
29.
Tang Q, Henriksen KJ, Bi M, Finger EB, Szot G, Ye J et al (2004) In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 199:1455–1465PubMedPubMedCentralCrossRef
30.
Sarween N, Chodos A, Raykundalia C, Khan M, Abbas AK, Walker LS (2004) CD4+CD25+ cells controlling a pathogenic CD4 response inhibit cytokine differentiation, CXCR-3 expression, and tissue invasion. J Immunol (Baltimore, Md: 1950) 173:2942–2951CrossRef
31.
Jaeckel E, von Boehmer H, Manns MP (2005) Antigen-specific FoxP3-transduced T-cells can control established type 1 diabetes. Diabetes 54:306–310PubMedCrossRef
32.
Piccirillo CA, Letterio JJ, Thornton AM, McHugh RS, Mamura M, Mizuhara H et al (2002) CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J Exp Med 196:237–246PubMedPubMedCentralCrossRef
33.
Weber SE, Harbertson J, Godebu E, Mros GA, Padrick RC, Carson BD et al (2006) Adaptive islet-specific regulatory CD4 T cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivo. J Immunol (Baltimore, Md: 1950) 176:4730–4739CrossRef
34.
Van YH, Lee WH, Ortiz S, Lee MH, Qin HJ, Liu CP (2009) All-trans retinoic acid inhibits type 1 diabetes by T regulatory (Treg)-dependent suppression of interferon-gamma-producing T-cells without affecting Th17 cells. Diabetes 58:146–155PubMedPubMedCentralCrossRef
35.
Bluestone JA (2005) Regulatory T-cell therapy: is it ready for the clinic? Nat Rev Immunol 5:343–349PubMedCrossRef
36.
Tritt M, Sgouroudis E (2008) d’Hennezel E, Albanese A, Piccirillo CA. Functional waning of naturally occurring CD4+ regulatory T-cells contributes to the onset of autoimmune diabetes. Diabetes 57:113–123PubMedCrossRef
37.
Tang Q, Adams JY, Tooley AJ, Bi M, Fife BT, Serra P et al (2006) Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol 7:83–92PubMedPubMedCentralCrossRef
38.
Feuerer M, Shen Y, Littman DR, Benoist C, Mathis D (2009) How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets. Immunity 31:654–664PubMedPubMedCentralCrossRef
39.
Zheng SG, Wang JH, Gray JD, Soucier H, Horwitz DA (2004) Natural and induced CD4+CD25+ cells educate CD4+CD25- cells to develop suppressive activity: the role of IL-2, TGF-beta, and IL-10. J Immunol (Baltimore, Md: 1950) 172:5213–5221CrossRef
40.
Tonkin DR, Haskins K (2009) Regulatory T cells enter the pancreas during suppression of type 1 diabetes and inhibit effector T cells and macrophages in a TGF-beta-dependent manner. Eur J Immunol 39:1313–1322PubMedPubMedCentralCrossRef
41.
Bluestone JA, Tang Q (2005) How do CD4+CD25+ regulatory T cells control autoimmunity? Curr Opin Immunol 17:638–642PubMedCrossRef
42.
Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z et al (2008) CTLA-4 control over Foxp3+ regulatory T cell function. Science (New York, NY) 322:271–275CrossRef
43.
Romo-Tena J, Gomez-Martin D, Alcocer-Varela J (2013) CTLA-4 and autoimmunity: new insights into the dual regulator of tolerance. Autoimmun Rev 12:1171–1176PubMedCrossRef
44.
Lee MH, Lee WH, Todorov I, Liu CP (2010) CD4+ CD25+ regulatory T cells prevent type 1 diabetes preceded by dendritic cell-dominant invasive insulitis by affecting chemotaxis and local invasiveness of dendritic cells. J Immunol (Baltimore, Md: 1950) 185:2493–2501CrossRef
45.
Cottrez F, Groux H (2001) Regulation of TGF-beta response during T cell activation is modulated by IL-10. J Immunol (Baltimore, Md: 1950) 167:773–778CrossRef
46.
Moore KW, de Waal MR, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765PubMedCrossRef
47.
Zhang J, Huang Z, Sun R, Tian Z, Wei H (2012) IFN-gamma induced by IL-12 administration prevents diabetes by inhibiting pathogenic IL-17 production in NOD mice. J Autoimmun 38:20–28PubMedCrossRef
48.
Scheffold A, Huhn J, Hofer T (2005) Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-)two to tango. Eur J Immunol 35:1336–1341PubMedCrossRef
49.
Edwards LJ, Evavold BD (2013) Destabilization of peptide:MHC interaction induces IL-2 resistant anergy in diabetogenic T cells. J Autoimmun 44:82–90PubMedCrossRef
50.
Peng H, Tian Z. NK (2013) Cell trafficking in health and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol
51.
Kachapati K, Bednar KJ, Adams DE, Wu Y, Mittler RS, Jordan MB et al (2013) Recombinant soluble CD137 prevents type one diabetes in nonobese diabetic mice. J Autoimmun 47:94–103PubMedCrossRef
52.
53.
Ryba M, Rybarczyk-Kapturska K, Zorena K, Mysliwiec M, Mysliwska J (2011) Lower frequency of CD62L(high) and higher frequency of TNFR2(+) Tregs are associated with inflammatory conditions in type 1 diabetic patients. Mediat Inflamm 2011:645643CrossRef
54.
Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree TI (2005) Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 54:92–99PubMedCrossRef
55.
Putnam AL, Vendrame F, Dotta F, Gottlieb PA (2005) CD4+CD25high regulatory T cells in human autoimmune diabetes. J Autoimmun 24:55–62PubMedCrossRef
56.
Luczynski W, Wawrusiewicz-Kurylonek N, Stasiak-Barmuta A, Urban R, Ilendo E, Urban M et al (2009) Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes. Acta Biochim Pol 56:361–370PubMed
57.
Lawson JM, Tremble J, Dayan C, Beyan H, Leslie RD, Peakman M et al (2008) Increased resistance to CD4+CD25hi regulatory T cell-mediated suppression in patients with type 1 diabetes. Clin Exp Immunol 154:353–359PubMedPubMedCentralCrossRef
58.
Brusko TM, Wasserfall CH, Clare-Salzler MJ, Schatz DA, Atkinson MA (2005) Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes. Diabetes 54:1407–1414PubMedCrossRef
59.
Schneider A, Rieck M, Sanda S, Pihoker C, Greenbaum C, Buckner JH (2008) The effector T cells of diabetic subjects are resistant to regulation via CD4+ FOXP3+ regulatory T cells. J Immunol (Baltimore, Md: 1950) 181:7350–7355CrossRef
60.
Monti P, Scirpoli M, Maffi P, Piemonti L, Secchi A, Bonifacio E et al (2008) Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+FOXP3+ regulatory T-cells. Diabetes 57:2341–2347PubMedPubMedCentralCrossRef
61.
Glisic-Milosavljevic S, Waukau J, Jailwala P, Jana S, Khoo HJ, Albertz H et al (2007) At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the CD4+CD25+ T-cell fraction. PLoS One 2:e146PubMedPubMedCentralCrossRef
62.
Hughson A, Bromberg I, Johnson B, Quataert S, Jospe N, Fowell DJ (2011) Uncoupling of proliferation and cytokines from suppression within the CD4+CD25+Foxp3+ T-cell compartment in the 1st year of human type 1 diabetes. Diabetes 60:2125–2133PubMedPubMedCentralCrossRef
63.
Glisic S, Ehlenbach S, Jailwala P, Waukau J, Jana S, Ghosh S (2010) Inducible regulatory T cells (iTregs) from recent-onset type 1 diabetes subjects show increased in vitro suppression and higher ITCH levels compared with controls. Cell Tissue Res 339:585–595PubMedCrossRef
64.
Ryba-Stanislawowska M, Skrzypkowska M, Mysliwska J, Mysliwiec M (2013) The serum IL-6 profile and Treg/Th17 peripheral cell populations in patients with type 1 diabetes. Mediat Inflamm 2013:205284CrossRef
65.
McClymont SA, Putnam AL, Lee MR, Esensten JH, Liu W, Hulme MA et al (2011) Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes. J Immunol (Baltimore, Md: 1950) 186:3918–3926CrossRef
66.
Du W, Shen YW, Lee WH, Wang D, Paz S, Kandeel F et al (2013) Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals. PLoS One 8:e56209PubMedPubMedCentralCrossRef
67.
Brusko T, Wasserfall C, McGrail K, Schatz R, Viener HL, Schatz D et al (2007) No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes. Diabetes 56:604–612PubMedCrossRef
68.
Marwaha AK, Crome SQ, Panagiotopoulos C, Berg KB, Qin H, Ouyang Q et al (2010) Cutting edge: increased IL-17-secreting T cells in children with new-onset type 1 diabetes. J Immunol (Baltimore, Md: 1950) 185:3814–3818CrossRef
69.
Alonso N, Martinez-Arconada MJ, Granada ML, Soldevila B, Canton A, Mate JL et al (2009) Regulatory T cells in type 1 diabetic patients with autoimmune chronic atrophic gastritis. Endocrine 35:420–428PubMedCrossRef
70.
Haseda F, Imagawa A, Murase-Mishiba Y, Terasaki J, Hanafusa T (2013) CD4(+) CD45RA(-) FoxP3high activated regulatory T cells are functionally impaired and related to residual insulin-secreting capacity in patients with type 1 diabetes. Clin Exp Immunol 173:207–216PubMedPubMedCentralCrossRef
71.
Badami E, Sorini C, Coccia M, Usuelli V, Molteni L, Bolla AM et al (2011) Defective differentiation of regulatory FoxP3+ T cells by small-intestinal dendritic cells in patients with type 1 diabetes. Diabetes 60:2120–2124PubMedPubMedCentralCrossRef
72.
Ferraro A, Socci C, Stabilini A, Valle A, Monti P, Piemonti L et al (2011) Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes. Diabetes 60:2903–2913PubMedPubMedCentralCrossRef
73.
Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S et al (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203:1701–1711PubMedPubMedCentralCrossRef
74.
Komatsu N, Mariotti-Ferrandiz ME, Wang Y, Malissen B, Waldmann H, Hori S (2009) Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc Natl Acad Sci U S A 106:1903–1908PubMedPubMedCentralCrossRef
75.
Yang XO, Nurieva R, Martinez GJ, Kang HS, Chung Y, Pappu BP et al (2008) Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29:44–56PubMedPubMedCentralCrossRef
76.
Long SA, Cerosaletti K, Bollyky PL, Tatum M, Shilling H, Zhang S et al (2010) Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4(+)CD25(+) regulatory T-cells of type 1 diabetic subjects. Diabetes 59:407–415PubMedPubMedCentralCrossRef
77.
78.
Nti BK, Markman JL, Bertera S, Styche AJ, Lakomy RJ, Subbotin VM et al (2012) Treg cells in pancreatic lymph nodes: the possible role in diabetogenesis and beta cell regeneration in a T1D model. Cell Mol Immunol 9:455–463PubMedPubMedCentralCrossRef
79.
Green EA, Choi Y, Flavell RA (2002) Pancreatic lymph node-derived CD4(+)CD25(+) Treg cells: highly potent regulators of diabetes that require TRANCE-RANK signals. Immunity 16:183–191PubMedCrossRef
80.
Montane J, Bischoff L, Soukhatcheva G, Dai DL, Hardenberg G, Levings MK et al (2011) Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets. J Clin Invest 121:3024–3028PubMedPubMedCentralCrossRef
81.
Beaudoin L, Diana J, Ghazarian L, Simoni Y, Boitard C, Lehuen A. (2014) Plasmacytoid dendritic cells license regulatory T cells, upon iNKT-cell stimulation, to prevent autoimmune diabetes. European journal of immunology
82.
Luo X, Tarbell KV, Yang H, Pothoven K, Bailey SL, Ding R et al (2007) Dendritic cells with TGF-beta1 differentiate naive CD4+CD25− T cells into islet-protective Foxp3+ regulatory T cells. Proc Natl Acad Sci U S A 104:2821–2826PubMedPubMedCentralCrossRef
83.
Tarbell KV, Petit L, Zuo X, Toy P, Luo X, Mqadmi A et al (2007) Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J Exp Med 204:191–201PubMedPubMedCentralCrossRef
84.
Van Belle TL, Ling E, Haase C, Bresson D, Urso B, von Herrath MG (2013) NKG2D blockade facilitates diabetes prevention by antigen-specific Tregs in a virus-induced model of diabetes. J Autoimmun 40:66–73PubMedCrossRef
85.
Orban T, Farkas K, Jalahej H, Kis J, Treszl A, Falk B et al (2010) Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy. J Autoimmun 34:408–415PubMedPubMedCentralCrossRef
86.
Hjorth M, Axelsson S, Ryden A, Faresjo M, Ludvigsson J, Casas R (2011) GAD-alum treatment induces GAD65-specific CD4+CD25highFOXP3+ cells in type 1 diabetic patients. Clin Immunol (Orlando, Fla) 138:117–126CrossRef
87.
Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D et al (2005) A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes 54:1763–1769PubMedCrossRef
88.
Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G et al (2005) Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 352:2598–2608PubMedCrossRef
89.
Ludvigsson J, Faresjo M, Hjorth M, Axelsson S, Cheramy M, Pihl M et al (2008) GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med 359:1909–1920PubMedCrossRef
90.
Axelsson S, Cheramy M, Hjorth M, Pihl M, Akerman L, Martinuzzi E et al (2011) Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes. PLoS One 6:e29008PubMedPubMedCentralCrossRef
91.
Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM et al (2009) C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA : J Am Med Assoc 301:1573–1579CrossRef
92.
Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F et al (2007) Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA : J Am Med Assoc 297:1568–1576CrossRef
93.
Haller MJ, Wasserfall CH, Hulme MA, Cintron M, Brusko TM, McGrail KM et al (2011) Autologous umbilical cord blood transfusion in young children with type 1 diabetes fails to preserve C-peptide. Diabetes Care 34:2567–2569PubMedPubMedCentralCrossRef
94.
Haller MJ, Wasserfall CH, Hulme MA, Cintron M, Brusko TM, McGrail KM et al (2013) Autologous umbilical cord blood infusion followed by oral docosahexaenoic acid and vitamin D supplementation for C-peptide preservation in children with Type 1 diabetes. Biol Blood Marrow Transplant : J Am Soc Blood Marrow Transplant 19:1126–1129CrossRef
95.
Giannopoulou EZ, Puff R, Beyerlein A, von Luettichau I, Boerschmann H, Schatz D et al (2014) Effect of a single autologous cord blood infusion on beta-cell and immune function in children with new onset type 1 diabetes: a non-randomized, controlled trial. Pediatr Diabetes 15:100–109PubMedCrossRef
96.
Zhao Y, Jiang Z, Zhao T, Ye M, Hu C, Yin Z et al (2012) Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med 10:3PubMedPubMedCentralCrossRef
97.
Ishikawa H, Ochi H, Chen ML, Frenkel D, Maron R, Weiner HL (2007) Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody. Diabetes 56:2103–2109PubMedCrossRef
98.
Chatenoud L, Primo J, Bach JF (1997) CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol (Baltimore, Md: 1950) 158:2947–2954
99.
Daifotis AG, Koenig S, Chatenoud L, Herold KC (2013) Anti-CD3 clinical trials in type 1 diabetes mellitus. Clin Immunol (Orlando, Fla) 149:268–278CrossRef
100.
Herold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W et al (2013) Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes 62:3766–3774PubMedCrossRef
101.
Keymeulen B, Walter M, Mathieu C, Kaufman L, Gorus F, Hilbrands R et al (2010) Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia 53:614–623PubMedCrossRef
102.
Ludvigsson J, Krisky D, Casas R, Battelino T, Castano L, Greening J et al (2012) GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. N Engl J Med 366:433–442PubMedCrossRef
103.
Wherrett DK, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R et al (2011) Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. Lancet 378:319–327PubMedPubMedCentralCrossRef
104.
Chaillous L, Lefevre H, Thivolet C, Boitard C, Lahlou N, Atlan-Gepner C et al (2000) Oral insulin administration and residual beta-cell function in recent-onset type 1 diabetes: a multicentre randomised controlled trial. Diabete Insuline Orale group. Lancet 356:545–549PubMedCrossRef
105.
Ergun-Longmire B, Marker J, Zeidler A, Rapaport R, Raskin P, Bode B et al (2004) Oral insulin therapy to prevent progression of immune-mediated (type 1) diabetes. Ann N Y Acad Sci 1029:260–277PubMedCrossRef
106.
Huurman VA, van der Meide PE, Duinkerken G, Willemen S, Cohen IR, Elias D et al (2008) Immunological efficacy of heat shock protein 60 peptide DiaPep277 therapy in clinical type I diabetes. Clin Exp Immunol 152:488–497PubMedPubMedCentralCrossRef
107.
Dahan R, Gebe JA, Preisinger A, James EA, Tendler M, Nepom GT et al (2013) Antigen-specific immunomodulation for type 1 diabetes by novel recombinant antibodies directed against diabetes-associates auto-reactive T cell epitope. J Autoimmun 47:83–93PubMedCrossRef
108.
Zhao Y, Lin B, Darflinger R, Zhang Y, Holterman MJ, Skidgel RA (2009) Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice. PLoS One 4:e4226PubMedPubMedCentralCrossRef
109.
Mesples A, Majeed N, Zhang Y, Hu X (2013) Early immunotherapy using autologous adult stem cells reversed the effect of anti-pancreatic islets in recently diagnosed type 1 diabetes mellitus: preliminary results. Med Sci Monit:Int Med J Exp Clin Res 19:852–857CrossRef
110.
Ambery P, Donner TW, Biswas N, Donaldson J, Parkin J, Dayan CM (2014) Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study. DiabetMed:J Br Diabet Assoc 31:399–402
111.
Lazar L, Ofan R, Weintrob N, Avron A, Tamir M, Elias D et al (2007) Heat-shock protein peptide DiaPep277 treatment in children with newly diagnosed type 1 diabetes: a randomised, double-blind phase II study. Diabetes Metab Res Rev 23:286–291PubMedCrossRef
112.
Buzzetti R, Cernea S, Petrone A, Capizzi M, Spoletini M, Zampetti S et al (2011) C-peptide response and HLA genotypes in subjects with recent-onset type 1 diabetes after immunotherapy with DiaPep277: an exploratory study. Diabetes 60:3067–3072PubMedPubMedCentralCrossRef
113.
Gu W, Hu J, Wang W, Li L, Tang W, Sun S et al (2012) Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes. Diabetes Care 35:1413–1419PubMedPubMedCentralCrossRef
Metadata
Title
Alteration of Regulatory T Cells in Type 1 Diabetes Mellitus: A Comprehensive Review
Authors
Tingting Tan
Yufei Xiang
Christopher Chang
Zhiguang Zhou
Publication date
01-10-2014
Publisher
Springer US
Published in
Clinical Reviews in Allergy & Immunology / Issue 2/2014
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-014-8440-0

Other articles of this Issue 2/2014

Clinical Reviews in Allergy & Immunology 2/2014 Go to the issue

ReviewPaper

The Mechanisms and Applications of T Cell Vaccination for Autoimmune Diseases: a Comprehensive Review

Erratum

Erratum to: Molecular Mechanisms in Autoimmune Type 1 Diabetes: a Critical Review

ReviewPaper

Molecular Biology of Atopic Dermatitis

ReviewPaper

TLR2 and TLR4 in Autoimmune Diseases: a Comprehensive Review

ReviewPaper

Molecular Mechanisms in Autoimmune Type 1 Diabetes: a Critical Review

ReviewPaper

NK Cell Trafficking in Health and Autoimmunity:A Comprehensive Review
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Obesity Clinical Trial Summary

At a glance: The STEP trials

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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
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