Targeting regulatory T cells in the treatment of type 1 diabetes mellitus

Current Molecular Medicine

Volumn 12, Issue 10, 2012, Pages 1261-1272

  Cabrera, S M ^a   Rigby, M R ^a   Mirmira, R G ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Autoimmunity; Effector t cells; Regulatory t cells; Teffs; Tregs; Type 1 diabetes mellitus

Indexed keywords

ALA ALA; ALEFACEPT; CD28 ANTIGEN; CD40 LIGAND; CHAPERONIN 60; COMPLEMENT COMPONENT C3A; COMPLEMENT COMPONENT C5A; GLUTAMATE DECARBOXYLASE 65; GRANULOCYTE COLONY STIMULATING FACTOR; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 2; LANSOPRAZOLE; MONOCLONAL ANTIBODY; OTELIXIZUMAB; RAPAMYCIN; SITAGLIPTIN; TEPLIZUMAB; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

AUTOIMMUNE DISEASE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; COMPLEMENT SYSTEM; DENDRITIC CELL; EFFECTOR CELL; HOMEOSTASIS; HUMAN; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; LOW DRUG DOSE; LYMPHOCYTIC INFILTRATION; NONHUMAN; PANCREAS ISLET BETA CELL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REGULATORY T LYMPHOCYTE; REVIEW; SIGNAL TRANSDUCTION; TH17 CELL;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, CD3; AUTOIMMUNITY; DENDRITIC CELLS; DIABETES MELLITUS, TYPE 1; IMMUNE TOLERANCE; INSULIN-SECRETING CELLS; INTERLEUKIN-10; MICE; RECOMBINANT FUSION PROTEINS; SIROLIMUS; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA;

ERAGROSTIS TEF; MUS;

EID: 84870225003     PISSN: 15665240     EISSN: 18755666     Source Type: Journal    
DOI: 10.2174/156652412803833634     Document Type: Review

References (155)

1. Anderson MS, Bluestone JA. The NOD mouse: a model of immune dysregulation. Annu Rev Immunol 2005;23: 447-485.
2. Lehuen A, Diana J, Zaccone P, Cooke A. Immune cell crosstalk in type 1 diabetes. Nat Rev Immunol 2010; 10(7): 501-513.
3. Effects of age, duration and treatment of insulin-dependent diabetes mellitus on residual beta-cell function: observations during eligibility testing for the Diabetes Control and Complications Trial (DCCT). The DCCT Research Group. J Clin Endocrinol Metab 1987; 65(1): 30-36.
4. Pozzilli P, Visalli N, Buzzetti R, et al. Metabolic and immune parameters at clinical onset of insulin-dependent diabetes: a population-based study. IMDIAB Study Group. Immunotherapy Diabetes. Metabolism 1998; 47(10): 1205-1210.
5. Rother KI, Spain LM, Wesley RA, et al. Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes. Diabetes Care 2009; 32(12): 2251-2257.
6. Mordes JP, Bortell R, Doukas J, et al. The BB/Wor rat and the balance hypothesis of autoimmunity. Diabetes Metab Rev 1996; 12(2): 103-109.
7. Bluestone JA, Tang Q, Sedwick CE. T regulatory cells inautoimmune diabetes: past challenges, future prospects. J Clin Immunol 2008; 28(6): 677-684.
8. Bour-Jordan H, Salomon BL, Thompson HL, Szot GL, Bernhard MR, Bluestone JA. Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells. J Clin Invest 2004; 114(7): 979-987.
9. Rigby MR, Trexler AM, Pearson TC, Larsen CP. CD28/CD154 blockade prevents autoimmune diabetes by inducing nondeletional tolerance after effector t-cell inhibition and regulatory T-cell expansion. Diabetes 2008; 57(10): 2672-2683.
10. Kojima A, Prehn RT. Genetic susceptibility to postthymectomy autoimmune diseases in mice. Immunogenetics 1981; 14(1-2): 15-27.
11. Sakaguchi S, Fukuma K, Kuribayashi K, Masuda T. Organspecific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med 1985; 161(1): 72-87.
12. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol 2008; 9(3): 239-244.
13. You S, Thieblemont N, Alyanakian MA, Bach JF, Chatenoud L. Transforming growth factor-beta and T-cell-mediated immunoregulation in the control of autoimmune diabetes. Immunol Rev 2006; 212: 185-202.
14. Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 2005; 6(11): 1142-1151.
15. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299(5609): 1057-1061.
16. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003; 4(4): 337-342.
17. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001; 27(1): 20-21.
18. Gambineri E, Torgerson TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol 2003; 15(4): 430-435.
19. Ochs HD, Ziegler SF, Torgerson TR. FOXP3 acts as arheostat of the immune response. Immunol Rev 2005; 203: 156-164.
20. Josefowicz SZ, Rudensky A. Control of regulatory T cell lineage commitment and maintenance. Immunity 2009;30(5): 616-625.
21. Curotto de Lafaille MA, Lafaille JJ. Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 2009; 30(5): 626-635.
22. Groux H, O'Garra A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389(6652): 737-742.
23. Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003; 198(12): 1875-1886.
24. Li MO, Sanjabi S, Flavell RA. Transforming growth factorbeta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 2006; 25(3): 455-471.
25. Marie JC, Letterio JJ, Gavin M, Rudensky AY. TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med 2005; 201(7): 1061-1067.
26. Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 1999; 190(7): 995-1004.
27. Fahlen L, Read S, Gorelik L, et al. T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells. J Exp Med 2005; 201(5): 737-746.
28. Nakamura K, Kitani A, Strober W. Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med 2001; 194(5): 629-644.
29. Cao X, Cai SF, Fehniger TA, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 2007; 27(4): 635-646.
30. Zhao DM, Thornton AM, DiPaolo RJ, Shevach EM. Activated CD4+CD25+ T cells selectively kill B lymphocytes. Blood 2006; 107(10): 3925-3932.
31. Almeida AR, Legrand N, Papiernik M, Freitas AA. Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL- 2 shape a population of regulatory cells that controls CD4+ T cell numbers. J Immunol 2002; 169(9): 4850-4860.
32. Furtado GC, Curotto de Lafaille MA, Kutchukhidze N, Lafaille JJ. Interleukin 2 signaling is required for CD4(+) regulatory T cell function. J Exp Med 2002; 196(6): 851-857.
33. Malek TR. The biology of interleukin-2. Annu Rev Immunol 2008; 26: 453-479.
34. Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 2007; 204(8): 1757-164.
35. Hsieh CS, Liang Y, Tyznik AJ, Self SG, Liggitt D, Rudensky AY. Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors. Immunity 2004; 21(2): 267-277.
36. Jordan MS, Boesteanu A, Reed AJ, et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist selfpeptide. Nat Immunol 2001; 2(4): 301-306.
37. Grinberg-Bleyer Y, Saadoun D, Baeyens A, et al. Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs. J Clin Invest 2010; 120(12): 4558-4568.
38. Grinberg-Bleyer Y, Baeyens A, You S, et al. IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells. J Exp Med 2010; 207(9): 1871-1878.
39. Chatenoud L, Primo J, Bach JF. CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol 1997; 158(6): 2947-2954.
40. Chatenoud L, Thervet E, Primo J, Bach JF. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci USA 1994; 91(1): 123-127.
41. Hering BJ, Kandaswamy R, Harmon JV, et al. Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody. Am J Transplant 2004; 4(3): 390-401.
42. Herold KC, Gitelman SE, Masharani U, et al. 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 2005; 54(6): 1763-1769.
43. Kaufman DL, Clare-Salzler M, Tian J, et al. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature 1993; 366(6450): 69-72.
44. Sgouroudis E, Piccirillo CA. Control of type 1 diabetes by CD4+Foxp3+ regulatory T cells: lessons from mouse models and implications for human disease. Diabetes Metab Res Rev 2009; 25(3): 208-218.
45. Tritt M, Sgouroudis E, d'Hennezel E, Albanese A, Piccirillo CA. Functional waning of naturally occurring CD4+ regulatory T-cells contributes to the onset of autoimmune diabetes. Diabetes 2008; 57(1): 113-123.
46. Pop SM, Wong CP, Culton DA, Clarke SH, Tisch R. Single cell analysis shows decreasing FoxP3 and TGFbeta1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetes. J Exp Med 2005; 201(8): 1333-1346.
47. Kumanogoh A, Wang X, Lee I, et al. Increased T cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T cell development. J Immunol 2001; 166(1): 353-360.
48. Salomon B, Lenschow DJ, Rhee L, et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 2000; 12(4): 431-440.
49. Tang Q, Henriksen KJ, Boden EK, et al. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol 2003; 171(7): 3348-3352.
50. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995; 3(5): 541-547.
51. Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 1995; 270(5238): 985-988.
52. Bending D, De la Pena H, Veldhoen M, et al. Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. J Clin Invest 2009; 119(3): 565-572.
53. van den Brandt J, Fischer HJ, Walter L, Hunig T, Kloting I, Reichardt HM. Type 1 diabetes in BioBreeding rats is critically linked to an imbalance between Th17 and regulatory T cells and an altered TCR repertoire. J Immunol 2010; 185(4): 2285-2294.
54. Haskins K, Cooke A. CD4 T cells and their antigens in the pathogenesis of autoimmune diabetes. Curr Opin Immunol 2011; 23(6): 739-745.
55. Cooke A. Th17 cells in inflammatory conditions. Rev Diabet Stud 2006; 3(2): 72-75.
56. Emamaullee JA, Davis J, Merani S, et al. Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes 2009; 58(6): 1302-1311.
57. Dendrou CA, Wicker LS. The IL-2/CD25 pathway determines susceptibility to T1D in humans and NOD mice. J Clin Immunol 2008; 28(6): 685-696.
58. Herold KC, Brooks-Worrell B, Palmer J, et al. Validity and reproducibility of measurement of islet autoreactivity by T-cell assays in subjects with early type 1 diabetes. Diabetes 2009; 58(11): 2588-2595.
59. Janson PC, Winerdal ME, Marits P, Thorn M, Ohlsson R, Winqvist O. FOXP3 promoter demethylation reveals the committed Treg population in humans. PLoS One 2008; 3(2): e1612.
60. Nagar M, Vernitsky H, Cohen Y, et al. Epigenetic inheritance of DNA methylation limits activation-induced expression of FOXP3 in conventional human CD25-CD4+ T cells. Int Immunol 2008; 20(8): 1041-1055.
61. Baron U, Floess S, Wieczorek G, et al. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. Eur J Immunol 2007; 37(9): 2378-2389.
62. Tree TI, Roep BO, Peakman M. A mini meta-analysis of studies on CD4+CD25+ T cells in human type 1 diabetes: report of the Immunology of Diabetes Society T Cell Workshop. Ann N Y Acad Sci 2006; 1079: 9-18.
63. Petrich de Marquesini LG, Fu J, Connor KJ, et al. IFNgamma and IL-10 islet-antigen-specific T cell responses in autoantibody-negative first-degree relatives of patients with type 1 diabetes. Diabetologia 2010; 53(7): 1451-1460.
64. Hughson A, Bromberg I, Johnson B, Quataert S, Jospe N, Fowell DJ. 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 2011; 60(8): 2125-2133.
65. Tang Q, Adams JY, Penaranda C, et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 2008; 28(5): 687-697.
66. Yamazaki S, Iyoda T, Tarbell K, et al. Direct expansion of functional CD25+ CD4+ regulatory T cells by antigenprocessing dendritic cells. J Exp Med 2003; 198(2): 235-247.
67. Vuckovic S, Withers G, Harris M, et al. Decreased blood dendritic cell counts in type 1 diabetic children. Clin Immunol 2007; 123(3): 281-288.
68. Badami E, Sorini C, Coccia M, et al. Defective Differentiation of Regulatory FoxP3+ T Cells by Small-Intestinal Dendritic Cells in Patients With Type 1 Diabetes. Diabetes 2011; 60(8): 2120-2124.
69. Jiang H, Canfield SM, Gallagher MP, et al. HLA-E-restricted regulatory CD8(+) T cells are involved in development and control of human autoimmune type 1 diabetes. J Clin Invest 2010; 120(10): 3641-3650.
70. Zhao Y, Jiang Z, Zhao T, et al. Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med 2012; 10(1): 3.
71. Zhao Y, Lin B, Darflinger R, Zhang Y, Holterman MJ, Skidgel RA. Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice. PLoS One 2009; 4(1): e4226.
72. Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol 2003; 21: 685-711.
73. Wilczynski JR, Radwan M, Kalinka J. The characterization and role of regulatory T cells in immune reactions. Front Biosci 2008; 13: 2266-2274.
74. Steinman RM, Nussenzweig MC. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci USA 2002; 99(1): 351-358.
75. Steinman RM. The control of immunity and tolerance by dendritic cell. Pathol Biol (Paris) 2003; 51(2): 59-60.
76. Tarbell KV, Petit L, Zuo X, et al. Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J Exp Med 2007; 204(1): 191-201.
77. Luo X, Tarbell KV, Yang H, et al. Dendritic cells with TGFbeta1 differentiate naive CD4+CD25- T cells into isletprotective Foxp3+ regulatory T cells. Proc Natl Acad Sci USA. 2007; 104(8): 2821-2826.
78. Tarbell KV, Yamazaki S, Olson K, Toy P, Steinman RM. CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J Exp Med 2004; 199(11): 1467-1477.
79. Cheatem D, Ganesh BB, Gangi E, Vasu C, Prabhakar BS. Modulation of dendritic cells using granulocyte-macrophage colony-stimulating factor (GM-CSF) delays type 1 diabetes by enhancing CD4+CD25+ regulatory T cell function. Clin Immunol 2009; 131(2): 260-270.
80. Gaudreau S, Guindi C, Menard M, Besin G, Dupuis G, Amrani A. Granulocyte-macrophage colony-stimulating factor prevents diabetes development in NOD mice by inducing tolerogenic dendritic cells that sustain the suppressive function of CD4+CD25+ regulatory T cells. J Immunol 2007; 179(6): 3638-3647.
81. Li Q, Nacion K, Bu H, Lin F. The complement inhibitor FUT- 175 suppresses T cell autoreactivity in experimental autoimmune encephalomyelitis. Am J Pathol 2009; 175(2): 661-667.
82. Liu J, Lin F, Strainic MG, et al. IFN-gamma and IL-17 production in experimental autoimmune encephalomyelitis depends on local APC-T cell complement production. J Immunol 2008; 180(9): 5882-5889.
83. Gao X, Liu H, Ding G, et al. Complement C3 deficiency prevent against the onset of streptozotocin-induced autoimmune diabetes involving expansion of regulatory T cells. Clin Immunol 2011; 140(3): 236-243.
84. Peng Q, Li K, Anderson K, et al. Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a-C3aR interaction. Blood 2008; 111(4): 2452-2461.
85. Weaver DJ, Jr., Reis ES, Pandey MK, et al. C5a receptordeficient dendritic cells promote induction of Treg and Th17 cells. Eur J Immunol 2010; 40(3): 710-721.
86. Lin M, Yin N, Murphy B, et al. Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin. Diabetes 2010; 59(9): 2247-2252.
87. Holler E, Roncarolo MG, Hintermeier-Knabe R, et al. Prognostic significance of increased IL-10 production in patients prior to allogeneic bone marrow transplantation. Bone Marrow Transplant 2000; 25(3): 237-241.
88. Baker KS, Roncarolo MG, Peters C, Bigler M, DeFor T, Blazar BR. High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths. Bone Marrow Transplant 1999; 23(11): 1123-1129.
89. Lin MT, Storer B, Martin PJ, et al. Relation of an interleukin- 10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med 2003; 349(23): 2201-2210.
90. VanBuskirk AM, Burlingham WJ, Jankowska-Gan E, et al. Human allograft acceptance is associated with immune regulation. J Clin Invest 2000; 106(1): 145-155.
91. Arif S, Tree TI, Astill TP, et al. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J Clin Invest 2004; 113(3): 451-463.
92. Durinovic-Bello I, Schlosser M, Riedl M, et al. Pro- and anti-inflammatory cytokine production by autoimmune T cells against preproinsulin in HLA-DRB1*04, DQ8 Type 1 diabetes. Diabetologia 2004; 47(3): 439-450.
93. Sanda S, Roep BO, von Herrath M. Islet antigen specific IL- 10+ immune responses but not CD4+CD25+FoxP3+ cells at diagnosis predict glycemic control in type 1 diabetes. Clin Immunol 2008; 127(2): 138-443.
94. Koh JJ, Ko KS, Lee M, Han S, Park JS, Kim SW. Degradable polymeric carrier for the delivery of IL-10 plasmid DNA to prevent autoimmune insulitis of NOD mice. Gene Ther 2000; 7(24): 2099-2104.
95. Wogensen L, Lee MS, Sarvetnick N. Production of interleukin 10 by islet cells accelerates immune-mediated destruction of beta cells in nonobese diabetic mice. J Exp Med 1994; 179(4): 1379-1384.
96. Tai N, Yasuda H, Xiang Y, et al. IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice. Clin Immunol 2011; 139(3): 336-349.
97. Lee MS, Wogensen L, Shizuru J, Oldstone MB, Sarvetnick N. Pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction. J Clin Invest 1994; 93(3): 1332-1338.
98. Azar ST, Salti I, Zantout MS, Major S. Alterations in plasma transforming growth factor beta in normoalbuminuric type 1 and type 2 diabetic patients. J Clin Endocrinol Metab 2000; 85(12): 4680-4682.
99. Olivieri A, De Angelis S, Dionisi S, et al. Serum transforming growth factor beta1 during diabetes development in nonobese diabetic mice and humans. Clin Exp Immunol 2010; 162(3): 407-414.
100. Grewal IS, Grewal KD, Wong FS, et al. Expression of transgene encoded TGF-beta in islets prevents autoimmune diabetes in NOD mice by a local mechanism. J Autoimmun 2002; 19(1-2): 9-22.
101. King C, Davies J, Mueller R, et al. TGF-beta1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype. Immunity 1998; 8(5): 601-613.
102. Drucker DJ. The biology of incretin hormones. Cell Metab 2006; 3(3): 153-165.
103. Hadjiyanni I, Baggio LL, Poussier P, Drucker DJ. Exendin-4 modulates diabetes onset in nonobese diabetic mice. Endocrinology 2008; 149(3): 1338-1349.
104. Zhang J, Tokui Y, Yamagata K, et al. Continuous stimulation of human glucagon-like peptide-1 (7-36) amide in a mouse model (NOD) delays onset of autoimmune type 1 diabetes. Diabetologia 2007; 50(9): 1900-1909.
105. Sherry NA, Chen W, Kushner JA, et al. Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells. Endocrinology 2007; 148(11): 5136-5144.
106. Morimoto C, Schlossman SF. The structure and function of CD26 in the T-cell immune response. Immunol Rev 1998; 161: 55-70.
107. Yan S, Marguet D, Dobers J, Reutter W, Fan H. Deficiency of CD26 results in a change of cytokine and immunoglobulin secretion after stimulation by pokeweed mitogen. Eur J Immunol 2003; 33(6): 1519-1527.
108. Reinhold D, Bank U, Buhling F, et al. Inhibitors of dipeptidyl peptidase IV induce secretion of transforming growth factorbeta 1 in PWM-stimulated PBMC and T cells. Immunology 1997; 91(3): 354-360.
109. Reinhold D, Bank U, Buhling F, et al. Inhibitors of dipeptidyl peptidase IV (DP IV, CD26) induces secretion of transforming growth factor-beta 1 (TGF-beta 1) in stimulated mouse splenocytes and thymocytes. Immunol Lett 1997; 58(1): 29-35.
110. Preller V, Gerber A, Wrenger S, et al. TGF-beta1-mediated control of central nervous system inflammation and autoimmunity through the inhibitory receptor CD26. J Immunol 2007; 178(7): 4632-4640.
111. Tian L, Gao J, Hao J, et al. Reversal of new-onset diabetes through modulating inflammation and stimulating beta-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor. Endocrinology 2010; 151(7): 3049-3060.
112. Belghith M, Bluestone JA, Barriot S, Megret J, Bach JF, Chatenoud L. TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Nat Med 2003; 9(9): 1202-1208.
113. Bisikirska B, Colgan J, Luban J, Bluestone JA, Herold KC. TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs. J Clin Invest 2005; 115(10): 2904-2913.
114. Bisikirska BC, Herold KC. Use of anti-CD3 monoclonal antibody to induce immune regulation in type 1 diabetes. Ann N Y Acad Sci 2004; 1037: 1-9.
115. Herold KC, Hagopian W, Auger JA, et al. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 2002; 346(22): 1692-1698.
116. Keymeulen B, Vandemeulebroucke E, Ziegler AG, et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 2005; 352(25): 2598-2608.
117. Ablamunits V, Bisikirska B, Herold KC. Acquisition of regulatory function by human CD8(+) T cells treated with anti-CD3 antibody requires TNF. Eur J Immunol 2010; 40(10): 2891-2901.
118. st Scientific Sessions; 2011 June 24-28, 2011; San Diego, California.
119. Sherry N, Hagopian W, Ludvigsson J, et al. Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial. Lancet 2011; 378(9790): 487-497.
120. Herold KC, Gitelman S, Greenbaum C, et al. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol 2009; 132(2): 166-173.
121. Ahmadzadeh M, Rosenberg SA. IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood 2006; 107(6): 2409-2414.
122. Zhang H, Chua KS, Guimond M, et al. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med 2005; 11(11): 1238-1243.
123. Wolf M, Schimpl A, Hunig T. Control of T cell hyperactivation in IL-2-deficient mice by CD4(+)CD25(-) and CD4(+)CD25(+) T cells: evidence for two distinct regulatory mechanisms. Eur J Immunol 2001; 31(6): 1637-1645.
124. Caudy AA, Reddy ST, Chatila T, Atkinson JP, Verbsky JW. CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes. J Allergy Clin Immunol 2007; 119(2): 482-487.
125. Yamanouchi J, Rainbow D, Serra P, et al. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet 2007; 39(3): 329-337.
126. Long SA, Cerosaletti K, Bollyky PL, et al. Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4(+)CD25(+) regulatory T-cells of type 1 diabetic subjects. Diabetes 2010; 59(2): 407-415.
127. Suntharalingam G, Perry MR, Ward S, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 2006; 355(10): 1018-1028.
128. Swee LK, Bosco N, Malissen B, Ceredig R, Rolink A. Expansion of peripheral naturally occurring T regulatory cells by Fms-like tyrosine kinase 3 ligand treatment. Blood 2009; 113(25): 6277-6287.
129. Hackstein H, Taner T, Logar AJ, Thomson AW. Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells. Blood 2002; 100(3): 1084-1087.
130. Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 2005; 105(12): 4743-4748.
131. Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo MG. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 2006; 177(12): 8338-8347.
132. Monti P, Scirpoli M, Maffi P, et al. Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+FOXP3+ regulatory T-cells. Diabetes 2008; 57(9): 2341-2347.
133. Battaglia M, Stabilini A, Draghici E, et al. Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance. Diabetes 2006; 55(1): 40-49.
134. Baekkeskov S, Nielsen JH, Marner B, Bilde T, Ludvigsson J, Lernmark A. Autoantibodies in newly diagnosed diabetic children immunoprecipitate human pancreatic islet cell proteins. Nature 1982; 298(5870):167-169.
135. Tian J, Atkinson MA, Clare-Salzler M, et al. Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulindependent diabetes. J Exp Med 1996; 183(4): 1561-1567.
136. Tian J, Clare-Salzler M, Herschenfeld A, et al. Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice. Nat Med 1996; 2(12): 1348-1353.
137. Tisch R, Liblau RS, Yang XD, Liblau P, McDevitt HO. Induction of GAD65-specific regulatory T-cells inhibits ongoing autoimmune diabetes in nonobese diabetic mice. Diabetes 1998; 47(6): 894-899.
138. Agardh CD, Cilio CM, Lethagen A, et al. Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes. J Diabetes Complications 2005; 19(4): 238-246.
139. Hjorth M, Axelsson S, Ryden A, Faresjo M, Ludvigsson J, Casas R. GAD-alum treatment induces GAD65-specific CD4+CD25highFOXP3+ cells in type 1 diabetic patients. Clin Immunol 2011; 138(1): 117-126.
140. Ludvigsson J, Faresjo M, Hjorth M, et al. GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med 2008; 359(18): 1909-1920.
141. Wherrett DK, Bundy B, Becker DJ, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomized double-blind trial. Lancet 2011; 378(9788): 319-327.
142. Krueger GG, Gottlieb AB, Sterry W, Korman N, Van De Kerkhof P. A multicenter, open-label study of repeat courses of intramuscular alefacept in combination with other psoriasis therapies in patients with chronic plaque psoriasis. J Dermatolog Treat 2008; 19(3): 146-155.
143. Menter A, Cather JC, Baker D, Farber HF, Lebwohl M, Darif M. The efficacy of multiple courses of alefacept in patients with moderate to severe chronic plaque psoriasis. J Am Acad Dermatol 2006; 54(1): 61-63.
144. Krueger GG. Selective targeting of T cell subsets: focus on alefacept - a remittive therapy for psoriasis. Expert Opin Biol Ther 2002; 2(4): 431-441.
145. Krueger GG, Callis KP. Development and use of alefacept to treat psoriasis. J Am Acad Dermatol 2003; 49(2 Suppl): S87-S97.
146. da Silva AJ, Brickelmaier M, Majeau GR, et al. Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol 2002; 168(9): 4462-4471.
147. Chamian F, Lin SL, Lee E, et al. Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis. J Transl Med 2007; 5: 27.
148. Ellis CN, Krueger GG. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001; 345(4): 248-255.
149. Weaver TA, Charafeddine AH, Agarwal A, et al. Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates. Nat Med 2009; 15(7): 746-749.
150. Orban T, Bundy B, Becker DJ, et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet 2011; 378(9789): 412-419.
151. Herold KC, Pescovitz MD, McGee P, et al. Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes. J Immunol 2011; 187(4): 1998-2005.
152. Zheng Q, Xu Y, Liu Y, et al. Induction of Foxp3 demethylation increases regulatory CD4+CD25+ T cells and prevents the occurrence of diabetes in mice. J Mol Med (Berl) 2009; 87(12): 1191-1205.
153. Chilton PM, Rezzoug F, Fugier-Vivier I, et al. Flt3-ligand treatment prevents diabetes in NOD mice. Diabetes 2004; 53(8): 1995-2002.
154. Morin J, Faideau B, Gagnerault MC, Lepault F, Boitard C, Boudaly S. Passive transfer of flt-3L-derived dendritic cells delays diabetes development in NOD mice and associates with early production of interleukin (IL)-4 and IL-10 in the spleen of recipient mice. Clin Exp Immunol 2003; 134(3): 388-395.
155. O'Keeffe M, Brodnicki TC, Fancke B, et al. Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development. Int Immunol 2005; 17(3): 307-314.