Clinical immunologic interventions for the treatment of type 1 diabetes

Cold Spring Harbor Perspectives in Medicine

Volumn 2, Issue 8, 2012, Pages

  Chatenoud, Lucienne ^a   Warncke, Katharina ^b,c   Ziegler, Anette G ^b,c  

^a UNIVERSITÉ PARIS DESCARTES   (France)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^c INSTITUTE OF EPIDEMIOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ABATACEPT; ANTIINFLAMMATORY AGENT; CALCITRIOL; CANAKINUMAB; CD3 ANTIBODY; CHAPERONIN 60; COLECALCIFEROL; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; ETANERCEPT; GLUTAMATE DECARBOXYLASE; IMMUNOSUPPRESSIVE AGENT; INSULIN; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; LYMPHOCYTE ANTIBODY; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; NICOTINAMIDE; OTELIXIZUMAB; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RITUXIMAB; TEPLIZUMAB; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; AUTOANTIGEN; MONOCLONAL ANTIBODY;

ARTICLE; AUTOLOGOUS BONE MARROW TRANSPLANTATION; CONTROLLED CLINICAL TRIAL (TOPIC); DRUG TARGETING; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; IMMUNOTHERAPY; INSULIN DEPENDENT DIABETES MELLITUS; MULTICENTER STUDY (TOPIC); NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); BONE MARROW TRANSPLANTATION; IMMUNOLOGY; METHODOLOGY; REVIEW;

ANTI-INFLAMMATORY AGENTS; ANTIBODIES, MONOCLONAL; ANTILYMPHOCYTE SERUM; AUTOANTIGENS; BONE MARROW TRANSPLANTATION; CHAPERONIN 60; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DIABETES MELLITUS, TYPE 1; GLUTAMATE DECARBOXYLASE; HUMANS; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; INSULIN;

EID: 84886696145     PISSN: None     EISSN: 21571422     Source Type: Journal    
DOI: 10.1101/cshperspect.a007716     Document Type: Article

References (105)

1. Achenbach P, Barker J, Bonifacio E, Pre Point Study Group. 2008. Modulating the natural history of type 1 diabetes in children at high genetic risk by mucosal insulin immunization. Curr Diab Rep 8: 87-93.
2. Agardh CD, Cilio CM, Lethagen A, Lynch K, Leslie RD, Palmer M, Harris RA, Robertson JA, Lernmark A. 2005. Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes. J Diabetes Complications 19: 238-246.
3. Alleva DG, Gaur A, Jin L, Wegmann D, Gottlieb PA, Pahuja A, Johnson EB, Motheral T, Putnam A, Crowe PD, et al. 2002. Immunological characterization and therapeutic activity of an altered-peptide ligand, NBI-6024, based on the immunodominant type 1 diabetes autoantigen insulin B-chain (9-23) peptide. Diabetes 51: 2126-2134.
4. Assan R, Feutren G, Debray-Sachs M, Quiniou-Debrie MC, Laborie C, ThomasG, Chatenoud L, Bach JF. 1985. Metabolic and immunological effects of cyclosporin in recently diagnosed type 1 diabetes mellitus. Lancet 1: 67-71.
5. Bach JF. 2011. Anti-CD3 antibodies for type 1 diabetes: Beyond expectations. Lancet 378: 459-460.
6. Bach JF, Chatenoud L. 2011. A historical view from thirty eventful years of immunotherapy in autoimmune diabetes. Semin Immunol 23: 174-181.
7. Baumgartl HJ, Standl E, Schmidt-Gayk H, Kolb HJ, Janka HU, Ziegler AG. 1991. Changes of vitamin D3 serum concentrations at the onset of immune-mediated type 1 (insulin-dependent) diabetes mellitus. Diabetes Res 16: 145-148.
8. Belghith M, Bluestone JA, Barriot S, Megret J, Bach JF, Chatenoud L. 2003. TGF-β-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Nat Med 9: 1202-1208.
9. Bierschenk L, Alexander J, Wasserfall C, Haller M, Schatz D, Atkinson M. 2009. Vitamin D levels in subjects with and without type 1 diabetes residing in a solar rich environment. Diabetes Care 32: 1977-1979.
10. Billingham RE, Brent L, Medawar PB. 1953. Actively acquired tolerance to foreign cells. Nature 172: 603-606.
11. Bluestone JA, St Clair EW, Turka LA. 2006. CTLA4Ig: Bridging the basic immunology with clinical application. Immunity 24: 233-238.
12. Brazelton TR, Morris RE. 1996. Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: Tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol 8: 710-720.
13. Chatenoud L. 2003. CD3-specific antibody-induced active tolerance: From bench to bedside. Nat Rev Immunol 3: 123-132.
14. Chatenoud L. 2010. Immune therapy for type 1 diabetes mellitus-What is unique about anti-CD3 antibodies? Nat Rev Endocrinol 6: 149-157.
15. Chatenoud L, Bluestone JA. 2007. CD3-specific antibodies: A portal to the treatment of autoimmunity. Nat Rev Immunol 7: 622-632.
16. Chatenoud L, Thervet E, Primo J, Bach JF. 1994. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci 91: 123-127.
17. Chatenoud L, Primo J, Bach JF. 1997. CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol 158: 2947-2954.
18. Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, MadeiraMI, Malmegrim KC, Foss-Freitas MC, Simoes BP, et al. 2009. C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA301: 1573-1579.
19. Diabetes Prevention Trial-Type 1 Diabetes Study Group. 2002. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346: 1685-1691.
20. Eisenbarth GS, Srikanta S, Jackson R, Rabinowe S, Dolinar R, Aoki T, Morris MA. 1985. Anti-thymocyte globulin and prednisone immunotherapy of recent onset type 1 diabetes mellitus. Diabetes Res 2: 271-276.
21. Eizirik DL, Colli ML, Ortis F. 2009. The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nat Rev Endocrinol 5: 219-226.
22. Elias D, Meilin A, Ablamunits V, Birk OS, Carmi P, Konenwaisman S, Cohen IR. 1997. Hsp60 peptide therapy of NOD mouse diabetes induces a Th2 cytokine burst and downregulates autoimmunity to various β-cell antigens. Diabetes 46: 758-764.
23. Feldmann M. 2002. Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol 2: 364-371.
24. Feutren G, Papoz L, Assan R, Vialettes B, Karsenty G, Vexiau P, Du Rostu H, Rodier M, Sirmai J, Lallemand A, et al. 1986. Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet 2: 119-124.
25. Fourlanos S, Perry C, Gellert SA, Martinuzzi E, Mallone R, Butler J, Colman PG, Harrison LC. 2011. Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes. Diabetes 60: 1237-1245.
26. Füchtenbusch M, Kredel K, Bonifacio E, Schnell O, Ziegler AG. 2000. Exposure to exogenous insulin promotes IgG1 and the T-helper 2-associated IgG4 responses to insulin but not to other islet autoantigens. Diabetes 49: 918-925.
27. Gottlieb PA, Quinlan S, Krause-Steinrauf H, Greenbaum CJ, Wilson DM, Rodriguez H, Schatz DA, Moran AM, Lachin JM, Skyler JS. 2010. Type 1 Diabetes TrialNet MMF/DZB Study Group. Failure to preserve β-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new-onset type 1 diabetes. Diabetes Care 33: 826-832.
28. Gysemans CA, Cardozo AK, Callewaert H, Giulietti A, Hulshagen L, Bouillon R, Eizirik DL, Mathieu C. 2005. 1, 25-Dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: Implications for prevention of diabetes in nonobese diabetic mice. Endocrinology 146: 1956-1964.
29. Hadaya K, Kared H, Masson A, Chatenoud L, Zavala F. 2005. G-CSF treatment prevents cyclophosphamide acceleration of autoimmune diabetes in the NOD mouse. J Autoimmun 24: 125-134.
30. Hannum CH, Wilcox CJ, Arend WP, Joslin FG, Dripps DJ, Heimdal PL, Armes LG, Sommer A, Eisenberg SP, Thompson RC. 1990. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature 343: 336-340.
31. Herold KC, Hagopian W, Auger JA, Poumian Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, et al. 2002. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 346: 1692-1698.
32. Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. 2005. A single course of anti-CD3 monoclonal antibody hOKT3γ1(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: 1763-1769.
33. Hirsch R, Bluestone JA, De Nenno L, Gress RE. 1990. Anti-CD3 F(ab′)2 fragments are immunosuppressive in vivo without evoking either the strong humoral response or morbidity associated with whole mAb. Transplantation 49: 1117-1123.
34. Hu CY, Rodriguez-Pinto D, Du W, Ahuja A, Henegariu O, Wong FS, ShlomchikMJ, Wen L. 2007. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J Clin Invest 117: 3857-3867.
35. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. 2001. Intake of vitamin D and risk of type 1 diabetes: A birth-cohort study. Lancet 358: 1500-1503.
36. Ikehara S. 1998. Bone marrow transplantation for autoimmune diseases. Acta Haematol 99: 116-132.
37. Ikehara S, Kawamura M, Takao F, Inaba M, Yasumizu R, Than S, Hisha H, Sugiura K, Koide Y, Yoshida TO, et al. 1990. Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells. Proc Natl Acad Sci 87: 8341-8344.
38. +regulatory T-cells. Diabetes 54: 78-84.
39. Kared H, Adle-Biassette H, Fois E, Masson A, Bach JF, Chatenoud L, SchneiderE, Zavala F. 2006. Jagged2-expressing hematopoietic progenitors promote regulatory T cell expansion in the periphery through notch signaling. Immunity 25: 823-834.
40. Kared H, Leforban B, Montandon R, Renand A, Layseca Espinosa E, ChatenoudL, Rosenstein Y, Schneider E, Dy M, Zavala F. 2008. Role of GM-CSF in tolerance induction by mobilized hematopoietic progenitors. Blood 112: 2575-2578.
41. Karussis DM, Slavin S, Ben-nun A, Ovadia H, Vourka-karussis U, Lehmann D, Mizrachi-kol R, Abramsky O. 1992a. Chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE): Treatment and induction of tolerance, with high dose cyclophosphamide followed by syngeneic bone marrow transplantation. J Neuroimmunol 39: 201-210.
42. Karussis DM, Slavin S, Lehmann D, Mizrachi-koll R, Abramsky O, Ben-nun A. 1992b. Prevention of experimental autoimmune encephalomyelitis and induction of tolerance with acute immunosuppression followed by syngeneic bone marrow transplantation. J Immunol 148: 1693-1698.
43. Karussis DM, Vourka-karussis U, Lehmann D, Ovadia H, Mizrachi-koll R, Ben-nun A, Abramsky O, Slavin S. 1993. Prevention and reversal of adoptively transferred, chronic relapsing experimental autoimmune encephalomyelitis with a single high dose cytoreductive treatment followed by syngeneic bone marrow transplantation. J Clin Invest 92: 765-772.
44. Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, HaleG, Gorus F, Goldman M, Walter M, Candon S, et al. 2005. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 352: 2598-2608.
45. Keymeulen B, Walter M, Mathieu C, Kaufman L, Gorus F, Hilbrands R, Vandemeulebroucke E, Van de Velde U, Crenier L, De Block C, 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 β cell mass. Diabetologia 53: 614-623.
46. + T cell unresponsiveness and functional reversal of established experimental autoimmune encephalomyelitis. J Immunol 174: 4525-4534.
47. Kremer JM, Westhovens R, Leon M, Di Giorgio E, Alten R, Steinfeld S, Russell A, Dougados M, Emery P, Nuamah IF, et al. 2003. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med 349: 1907-1915.
48. Kuhn C, You S, Valette F, Hale G, van Endert P, Bach JF, Waldmann H, Chatenoud L. 2011. Human CD3 transgenic mice: Preclinical testing of antibodies promoting immune tolerance. Sci Transl Med 3: 68ra10.
49. Kushida T, Inaba M, Takeuchi K, Sugiura K, Ogawa R, Ikehara S. 2000. Treatment of intractable autoimmune diseases in MRL/lpr mice using a new strategy for allogeneic bone marrow transplantation. Blood 95: 1862-1868.
50. Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. 2007. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 356: 1517-1526.
51. Lazar L, Ofan R, Weintrob N, Avron A, Tamir M, Elias D, Phillip M, Josefsberg Z. 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: 286-291.
52. Like AA, Rossini AA, Guberski DL, Appel MC, Williams RM. 1979. Spontaneous diabetes mellitus: Reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Science 206: 1421-1423.
53. Ludvigsson J, Faresjo M, Hjorth M, Axelsson S, Cheramy M, Pihl M, Vaarala O, Forsander G, Ivarsson S, Johansson C, et al. 2008. GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med 359: 1909-1920.
54. Ludvigsson J, Krisky D, Casas R, Battelino T, Castano L, Greening J, KordonouriO, Otonkoski T, Pozzilli P, Robert JJ. 2012. GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. N Engl J Med 366: 433-442.
55. Makhlouf L, Grey ST, Dong V, Csizmadia E, Arvelo MB, Auchincloss H Jr., Ferran C, Sayegh MH. 2004. Depleting anti-CD4 monoclonal antibody cures new-onset diabetes, prevents recurrent autoimmune diabetes, and delays allograft rejection in nonobese diabetic mice. Transplantation 77: 990-997.
56. Maki T, Ichikawa T, Blanco R, Porter J. 1992. Long-term abrogation of autoimmune diabetes in nonobese diabetic mice by immunotherapy with anti-lymphocyte serum. Proc Natl Acad Sci 89: 3434-3438.
57. Mandrup-Poulsen T. 1996. The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia 39: 1005-1029.
58. Mandrup-Poulsen T, Pickersgill L, Donath MY. 2010. Blockade of interleukin 1 in type 1 diabetes mellitus. Nat Rev Endocrinol 6: 158-166.
59. Marmont AM, Van Lint MT, Gualandi F, Bacigalupo A. 1997. Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration. Lupus 6: 545-548.
60. Martin S, Schernthaner G, Nerup J, Gries FA, Koivisto VA, Dupré J, Standl E, Hamet P, McArthur R, Tan MH, et al. 1991. Follow-up of cyclosporin A treatment in type 1 (insulin-dependent) diabetes mellitus: Lack of long-term effects. Diabetologia 34: 429-434.
61. Mastrandrea L, Yu J, Behrens T, Buchlis J, Albini C, Fourtner S, Quattrin T. 2009. Etanercept treatment in children with new-onset type 1 diabetes: Pilot randomized, placebo-controlled, double-blind study. Diabetes Care 32: 1244-1249.
62. Mathieu C, Gysemans C, Giulietti A, Bouillon R. 2005. Vitamin D and diabetes. Diabetologia 48: 1247-1257.
63. McAllister LD, Beatty PG, Rose J. 1997. Allogeneic bone marrow transplant for chronic myelogenous leukemia in a patient with multiple sclerosis. Bone Marrow Transplant 19: 395-397.
64. Monaco AP, Wood ML, Russell PS. 1966. Studies on heterologous antilymphocyte serum in mice. III. Immunological tolerance and chimerism produced across the H2-locus with adult thymectomy and antilymphocyte serum. Ann NY Acad Sci 129: 190-209.
65. Nanto-Salonen K, Kupila A, Simell S, Siljander H, Salonsaari T, Hekkala A, Korhonen S, Erkkola R, Sipila JI, Haavisto L, et al. 2008. Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: A double-blind, randomised controlled trial. Lancet 372: 1746-1755.
66. Ogilvie AL, Antoni C, Dechant C, Manger B, Kalden JR, Schuler G, Luftl M. 2001. Treatment of psoriatic arthritis with antitumour necrosis factor-α antibody clears skin lesions of psoriasis resistant to treatment with methotrexate. Br J Dermatol 144: 587-589.
67. Orban T, Bundy B, Becker DJ, Dimeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Marks JB, Monzavi R, et al. 2011. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: A randomised, double-blind, placebo-controlled trial. Lancet 378: 412-419.
68. Patterson CC, Dahlquist GG, Gyurus E, Green A, Soltesz G. 2009. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: A multicentre prospective registration study. Lancet 373: 2027-2033.
69. Penaranda C, Tang Q, Bluestone JA. 2011. Anti-CD3 therapy promotes tolerance by selectively depleting pathogenic cells while preserving regulatory T cells. J Immunol 187: 2015-2022.
70. Penna G, Amuchastegui S, Giarratana N, Daniel KC, Vulcano M, Sozzani S, Adorini L. 2007a. 1, 25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells. J Immunol 178: 145-153.
71. Penna G, Amuchastegui S, Laverny G, Adorini L. 2007b. Vitamin D receptor agonists in the treatment of autoimmune diseases: Selective targeting of myeloid but not plasmacytoid dendritic cells. J Bone Miner Res 22: V69-V73.
72. Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, McGee PF, Moran AM, et al. 2009. Rituximab, B-lymphocyte depletion, and preservation of β-cell function. N Engl J Med 361: 2143-2152.
73. Pitocco D, Crino A, Di Stasio E, Manfrini S, Guglielmi C, Spera S, AnguissolaGB, Visalli N, Suraci C, Matteoli MC, et al. 2006. The effects of calcitriol and nicotinamide on residual pancreatic β-cell function in patients with recent-onset type 1 diabetes (IMDIAB XI). Diabet Med 23: 920-923.
74. Raz I, Elias D, Avron A, Tamir M, Metzger M, Cohen IR. 2001. β-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): A randomised, double-blind, phase II trial. Lancet 358: 1749-1753.
75. Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR. 1994. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83: 435-445.
76. + natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 212: 8-27.
77. + immunoregulatory T cells that control autoimmune diabetes. Immunity 12: 431-440.
78. Saudek F, Havrdova T, Boucek P, Karasova L, Novota P, Skibova J. 2004. Polyclonal anti-T-cell therapy for type 1 diabetes mellitus of recent onset. Rev Diabet Stud 1: 80-88.
79. Schloot NC, Meierhoff G, Lengyel C, Vandorfi G, Takacs J, Panczel P, Barkai L, Madacsy L, Oroszlan T, Kovacs P, et al. 2007. Effect of heat shock protein peptide DiaPep277 on β-cell function in paediatric and adult patients with recent-onset diabetes mellitus type 1: Two prospective, randomized, double-blind phase II trials. Diabetes Metab Res Rev 23: 276-285.
80. Serreze DV, Chapman HD, Varnum DS, Hanson MS, Reifsnyder PC, Richard SD, Fleming SA, Leiter EH, Shultz LD. 1996. B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: Analysis of a new "speed congenic" stock of NOD. Ig mu(null) mice. J Exp Med 184: 2049-2053.
81. Sherry N, Hagopian W, Ludvigsson J, Jain SM, Wahlen J, Ferry RJ Jr., Bode B, Aronoff S, Holland C, Carlin C, et al. 2011. Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial. Lancet 378: 487-497.
82. Sigal NH, Dumont FJ. 1992. Cyclosporin A, FK-506, and rapamycin: Pharmacologic probes of lymphocyte signal transduction. Annu Rev Immunol 10: 519-560.
83. Simon G, Parker M, Ramiya V, Wasserfall C, Huang Y, Bresson D, Schwartz RF, Campbell-Thompson M, Tenace L, Brusko T, et al. 2008. Murine antithymocyte globulin therapy alters disease progression in NOD mice by a time-dependent induction of immunoregulation. Diabetes 57: 405-414.
84. Sreenan S, Pick AJ, Levisetti M, Baldwin AC, Pugh W, Polonsky KS. 1999. Increased β-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse. Diabetes 48: 989-996.
85. Stiller CR, Dupre J, Gent M, Jenner MA, Keown PA, Laupacis A, Martell R, RodgerNW, Von Graffenried B, Wolfe BM. 1984. Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset. Science 223: 1362-1367.
86. + regulatory T cells. J Immunol 171: 3348-3352.
87. The Canadian-European Randomized Control Trial Group. 1988. Cyclosporin-induced remission of IDDM after early intervention. Association of 1 yr of cyclosporin treatment with enhanced insulin secretion. Diabetes 37: 1574-1582.
88. Thrower SL, James L, Hall W, Green KM, Arif S, Allen JS, Van Krinks C, Lozanoska-Ochser B, Marchesini L, Brown S, et al. 2009. Proinsulin peptide immunotherapy in type 1 diabetes: Report of a first-in-man Phase I safety study. Clin Exp Immunol 155: 156-165.
89. Tian J, Atkinson MA, Clare Salzler M, Herschenfeld A, Forsthuber T, LehmannPV, Kaufman DL. 1996. Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. J Exp Med 183: 1561-1567.
90. Tisch R, Wang B, Serreze DV. 1999. Induction of glutamic acid decarboxylase 65-specific Th2 cells and suppression of autoimmune diabetes at late stages of disease is epitope dependent. J Immunol 163: 1178-1187.
91. Tyndall A, Gratwohl A. 1997. Bone marrow transplantation in the treatment of autoimmune diseases. Br J Rheumatol 36: 1-3.
92. Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P, NeylanJ, Wilkinson A, Ekberg H, Gaston R, et al. 1998. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N Engl J Med 338: 161-165.
93. Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B, Blancho G, Lang P, Grinyo J, Halloran PF, Solez K, et al. 2005. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 353: 770-781.
94. VIT D Eurodiab. 1999. Vitamin D supplement in early childhood and risk for type I (insulin-dependent) diabetes mellitus. The EURODIAB Substudy 2 Study Group. Diabetologia 42: 51-54.
95. Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simoes BP, et al. 2007. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 297: 1568-1576.
96. Walter M, Philotheou A, Bonnici F, Ziegler AG, Jimenez R. 2009. No effect of the altered-peptide ligand nbi-6024 on β cell residual function and insulin needs in new-onset type 1 diabetes. Diabetes Care 32: 2036-2040.
97. Walter M, Kaupper T, Adler K, Foersch J, Bonifacio E, Ziegler AG. 2010. No effect of the 1α, 25-dihydroxyvitamin D3 on β-cell residual function and insulin requirement in adults with new-onset type 1 diabetes. Diabetes Care 33: 1443-1438.
98. Wherrett DK, Bundy B, Becker DJ, Dimeglio LA, Gitelman SE, Goland R, GottliebAP, Greenbaum CJ, Herold KC, Marks JB, 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: 319-327.
99. Wojciechowski D, Vincenti F. 2011. Challenges and opportunities in targeting the costimulation pathway in solid organ transplantation. Semin Immunol 23: 157-164.
100. Wood ML, Monaco AP, Gozzo JJ, Liegeois A. 1971. Use of homozygous allogeneic bone marrow for induction of tolerance with antilymphocyte serum: Dose and timing. Transplant Proc 3: 676-679.
101. Yasumizu R, Sugiura K, Iwai H, Inaba M, Makino S, Ida T, Imura H, HamashimaY, Good RA, Ikehara S. 1987. Treatment of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue. Proc Natl Acad Sci 84: 6555-6557.
102. You S, Thieblemont N, Alyanakian MA, Bach JF, Chatenoud L. 2006. Transforming growth factor-β and T-cell-mediated immunoregulation in the control of autoimmune diabetes. Immunol Rev 212: 185-202.
103. You S, Leforban B, Garcia C, Bach JF, Bluestone JA, Chatenoud L. 2007. Adaptive TGF-β-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment. Proc Natl Acad Sci 104: 6335-6340.
104. Young NS, Calado RT, Scheinberg P. 2006. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108: 2509-2519.
105. Zipitis CS, Akobeng AK. 2008. Vitamin D supplementation in early childhood and risk of type 1 diabetes: A systematic review and meta-analysis. Arch Dis Child 93: 512-517.