Emerging immune therapies in type 1 diabetes and pancreatic islet transplantation

In type 1 diabetes (T1D) the immune system attacks insulin‐producing pancreatic β‐cells. Unfortunately, our ability to curb this pathogenic autoimmune response in a disease‐ and organ‐specific manner is still very limited due to the inchoate understanding of the exact nature and the kinetics of the...

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Veröffentlicht in:	Diabetes, obesity & metabolism Jg. 15; H. 7; S. 581 - 592
Hauptverfasser:	Schneider, D. A., Kretowicz, A. M., von Herrath, M. G.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Oxford, UK Blackwell Publishing Ltd 01.07.2013 Wiley Subscription Services, Inc
Schlagworte:	Animals Autoimmune diseases Autoimmunity beta cell Biomedical Research - trends clinical trial Diabetes diabetes mellitus Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - prevention & control Diabetes Mellitus, Type 1 - therapy Humans Immunotherapy - trends islets Islets of Langerhans Transplantation - immunology Islets of Langerhans Transplantation - trends Pancreas Pancreas - immunology Pancreas Transplantation - trends transplantation type 1 diabetes
ISSN:	1462-8902, 1463-1326, 1463-1326
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Abstract	In type 1 diabetes (T1D) the immune system attacks insulin‐producing pancreatic β‐cells. Unfortunately, our ability to curb this pathogenic autoimmune response in a disease‐ and organ‐specific manner is still very limited due to the inchoate understanding of the exact nature and the kinetics of the immunological pathomechanisms that lead to T1D. None of the clinical immune interventions thus far, which focused primarily on new‐onset disease, were successful in producing lasting remission or curbing recurrent autoimmunity. However, these studies do provide us access to a tremendous amount of clinical data and specimens, which will aid us in revising our therapeutical approaches and defining the highly needed paradigm shift in T1D immunotherapy. Analysing the foundation and the results of the most current T1D immunotherapeutic trials, this article gives an outlook for future directions of the field.
AbstractList	In type 1 diabetes (T1D) the immune system attacks insulin‐producing pancreatic β‐cells. Unfortunately, our ability to curb this pathogenic autoimmune response in a disease‐ and organ‐specific manner is still very limited due to the inchoate understanding of the exact nature and the kinetics of the immunological pathomechanisms that lead to T1D. None of the clinical immune interventions thus far, which focused primarily on new‐onset disease, were successful in producing lasting remission or curbing recurrent autoimmunity. However, these studies do provide us access to a tremendous amount of clinical data and specimens, which will aid us in revising our therapeutical approaches and defining the highly needed paradigm shift in T1D immunotherapy. Analysing the foundation and the results of the most current T1D immunotherapeutic trials, this article gives an outlook for future directions of the field. In type 1 diabetes (T1D) the immune system attacks insulin-producing pancreatic β-cells. Unfortunately, our ability to curb this pathogenic autoimmune response in a disease- and organ-specific manner is still very limited due to the inchoate understanding of the exact nature and the kinetics of the immunological pathomechanisms that lead to T1D. None of the clinical immune interventions thus far, which focused primarily on new-onset disease, were successful in producing lasting remission or curbing recurrent autoimmunity. However, these studies do provide us access to a tremendous amount of clinical data and specimens, which will aid us in revising our therapeutical approaches and defining the highly needed paradigm shift in T1D immunotherapy. Analysing the foundation and the results of the most current T1D immunotherapeutic trials, this article gives an outlook for future directions of the field.In type 1 diabetes (T1D) the immune system attacks insulin-producing pancreatic β-cells. Unfortunately, our ability to curb this pathogenic autoimmune response in a disease- and organ-specific manner is still very limited due to the inchoate understanding of the exact nature and the kinetics of the immunological pathomechanisms that lead to T1D. None of the clinical immune interventions thus far, which focused primarily on new-onset disease, were successful in producing lasting remission or curbing recurrent autoimmunity. However, these studies do provide us access to a tremendous amount of clinical data and specimens, which will aid us in revising our therapeutical approaches and defining the highly needed paradigm shift in T1D immunotherapy. Analysing the foundation and the results of the most current T1D immunotherapeutic trials, this article gives an outlook for future directions of the field. In type 1 diabetes (T1D) the immune system attacks insulin-producing pancreatic beta -cells. Unfortunately, our ability to curb this pathogenic autoimmune response in a disease- and organ-specific manner is still very limited due to the inchoate understanding of the exact nature and the kinetics of the immunological pathomechanisms that lead to T1D. None of the clinical immune interventions thus far, which focused primarily on new-onset disease, were successful in producing lasting remission or curbing recurrent autoimmunity. However, these studies do provide us access to a tremendous amount of clinical data and specimens, which will aid us in revising our therapeutical approaches and defining the highly needed paradigm shift in T1D immunotherapy. Analysing the foundation and the results of the most current T1D immunotherapeutic trials, this article gives an outlook for future directions of the field. In type 1 diabetes (T1D) the immune system attacks insulin-producing pancreatic [beta]-cells. Unfortunately, our ability to curb this pathogenic autoimmune response in a disease- and organ-specific manner is still very limited due to the inchoate understanding of the exact nature and the kinetics of the immunological pathomechanisms that lead to T1D. None of the clinical immune interventions thus far, which focused primarily on new-onset disease, were successful in producing lasting remission or curbing recurrent autoimmunity. However, these studies do provide us access to a tremendous amount of clinical data and specimens, which will aid us in revising our therapeutical approaches and defining the highly needed paradigm shift in T1D immunotherapy. Analysing the foundation and the results of the most current T1D immunotherapeutic trials, this article gives an outlook for future directions of the field. [PUBLICATION ABSTRACT]
Author	von Herrath, M. G. Kretowicz, A. M. Schneider, D. A.
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Cites_doi	10.1038/80516 10.1056/NEJMc1200978 10.2337/db10-1360 10.1001/jama.1963.73700220012020c 10.4049/jimmunol.1103298 10.1210/en.2007-0358 10.2337/db07-1331 10.1056/NEJM199711203372118 10.1056/NEJMoa043980 10.1016/j.clim.2004.03.007 10.1084/jem.20100209 10.2337/dc09-0054 10.4049/jimmunol.173.7.4331 10.1097/TP.0b013e3181fe1377 10.2337/db10-0676 10.1084/jem.20110574 10.1016/j.jaut.2010.10.005 10.2337/diabetes.54.1.92 10.1007/s00109-011-0757-z 10.7326/0003-4819-128-7-199804010-00001 10.1084/jem.20111187 10.1007/s00125-012-2753-4 10.2337/diabetes.55.04.06.db05-1261 10.1136/annrheumdis-2011-200690 10.1007/s00125-009-1390-z 10.2337/db12-0098 10.1111/j.1600-6143.2010.03073.x 10.1007/s00125-009-1642-y 10.2337/db10-1419 10.1056/NEJMoa1105143 10.1084/jem.176.6.1595 10.1056/NEJMoa0904452 10.1172/JCI28423 10.2337/db11-1033 10.2337/db08-0688 10.4049/jimmunol.163.11.6275 10.1900/RDS.2004.1.80 10.1152/ajpendo.00132.2010 10.1097/TP.0b013e3181a9ee6c 10.1172/JCI115946 10.1016/j.transproceed.2008.02.010 10.1172/JCI118919 10.1111/j.1399-5448.2011.00761.x 10.1111/j.1365-2249.2008.03860.x 10.1172/JCI0215488 10.1016/0167-5699(93)90163-F 10.1146/annurev.iy.10.040192.001101 10.1182/blood-2011-09-377051 10.2337/dc09-0449 10.2337/db07-0416 10.1084/jem.166.4.982 10.1073/pnas.91.1.123 10.1097/TP.0b013e31817efc78 10.1016/j.clim.2011.12.005 10.1016/j.jaut.2009.10.005 10.1515/JPEM.2001.14.9.1585 10.1046/j.1600-6143.2003.00351.x 10.4049/jimmunol.160.4.1717 10.1038/80525 10.1126/science.388619 10.1097/MED.0b013e32833aba41 10.1210/jc.81.12.4264 10.1016/j.humimm.2007.05.010 10.1073/pnas.0808031105 10.1073/pnas.89.8.3434 10.2337/dc11-0523 10.1172/JCI27191 10.2337/db12-0049 10.1111/j.1445-5994.1980.tb04101.x 10.2337/diab.46.5.758 10.1038/ni.1817 10.1038/nm1296-1348 10.1371/journal.pone.0033108 10.1016/j.bbrc.2007.11.077 10.1038/nm.2764 10.2337/db09-1378 10.1038/nm1673 10.1056/NEJM200007273430401 10.1016/j.semarthrit.2012.03.004 10.2337/dc12-0038 10.2337/diabetes.51.3.638 10.1016/S0140-6736(11)60980-X 10.2337/diabetes.54.5.1407 10.2337/db10-0560 10.1016/S1074-7613(00)80121-1 10.1056/NEJMoa0804328 10.1084/jem.20051224 10.2337/diabetes.52.8.1976 10.1097/TP.0b013e3181ff8772 10.1016/S0140-6736(11)60886-6 10.1056/NEJMoa012864 10.1111/j.1600-6143.2004.00589.x
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References	Posselt AM, Bellin MD, Tavakol M et al. Islet transplantation in type 1 diabetics using an immunosuppressive protocol based on the anti-LFA-1 antibody efalizumab. Am J Transplant 2010; 10: 1870-1880. Suarez-Pinzon WL, Cembrowski GS, Rabinovitch A. Combination therapy with a dipeptidyl peptidase-4 inhibitor and a proton pump inhibitor restores normoglycaemia in non-obese diabetic mice. Diabetologia 2009; 52: 1680-1682. Bielekova B, Goodwin B, Richert N et al. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand. Nat Med 2000; 6: 1167-1175. Machen J, Harnaha J, Lakomy R, Styche A, Trucco M, Giannoukakis N. Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J Immunol 2004; 173: 4331-4341. Suarez-Pinzon WL, Power RF, Yan Y, Wasserfall C, Atkinson M, Rabinovitch A. Combination therapy with glucagon-like peptide-1 and gastrin restores normoglycemia in diabetic NOD mice. Diabetes 2008; 57: 3281-3288. von Herrath MG, Dyrberg T, Oldstone MB. Oral insulin treatment suppresses virus-induced antigen-specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice. J Clin Invest 1996; 98: 1324-1331. Sorenby AK, Kumagai-Braesch M, Sharma A, Hultenby KR, Wernerson AM, Tibell AB. Preimplantation of an immunoprotective device can lower the curative dose of islets to that of free islet transplantation: studies in a rodent model. Transplantation 2008; 86: 364-366. Tarantal AF, Lee CC, Itkin-Ansari P. Real-time bioluminescence imaging of macroencapsulated fibroblasts reveals allograft protection in rhesus monkeys (Macaca mulatta). Transplantation 2009; 88: 38-41. Keenan HA, Sun JK, Levine J et al. Residual insulin production and pancreatic ss-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes 2010; 59: 2846-2853. Liddy N, Bossi G, Adams KJ et al. Monoclonal TCR-redirected tumor cell killing. Nat Med 2012; 18: 980-987. 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: 390-401. Schneider DA, Boettler T, von-Herrath MG. Novel approach to test for immune protecting properties of semipermeable membranes in pancreatic islet transplantation. Scientific Sessions of the American Diabetes Association. Philadelphia, 2012. Schneider DA, Sarikonda G, von Herrath MG. Combination therapy with InsB9-23 peptide immunization and CTLA4-IgG does not reverse diabetes in NOD mice. Clin Immunol 2012; 142: 402-403. Linsley PS, Greene JL, Tan P et al. Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J Exp Med 1992; 176: 1595-1604. Fourlanos S, Perry C, Gellert SA et al. Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes. Diabetes 2011; 60: 1237-1245. Jonker M, Ringers J, Kuhn EM, 't Hart B, Foulkes R. Treatment with anti-MHC-class-II antibody postpones kidney allograft rejection in primates but increases the risk of CMV activation. Am J Transplant 2004; 4: 1756-1761. Pileggi A, Molano RD, Song S et al. Alpha-1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts. Transplant Proc 2008; 40: 457-458. Bresson D, Togher L, Rodrigo E et al. Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. J Clin Invest 2006; 116: 1371-1381. Epstein WV. Treatment of rheumatoid arthritis with a tumor necrosis factor receptor-Fc fusion protein. N Engl J Med 1997; 337: 1559-1560; author reply 1560-1551. Michels AW, Nakayama M. The anti-insulin trimolecular complex in type 1 diabetes. Curr Opin Endocrinol Diabetes Obes 2010; 17: 329-334. Brusko TM, Wasserfall CH, Clare-Salzler MJ, Schatz DA, Atkinson MA. Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes. Diabetes 2005; 54: 1407-1414. Walter M, Philotheou A, Bonnici F, Ziegler AG, Jimenez R, Group NBIS. No effect of the altered peptide ligand NBI-6024 on beta-cell residual function and insulin needs in new-onset type 1 diabetes. Diabetes Care 2009; 32: 2036-2040. Shapiro AM, Lakey JR, Ryan EA et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343: 230-238. Buyukgebiz A, Cemeroglu AP, Bober E, Mohn A, Chiarelli F. Factors influencing remission phase in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2001; 14: 1585-1596. Nagler W, Taylor H. Diabetic coma with acute inflammation of Islets of Langerhans. JAMA 1963; 184: 723-725. Clare-Salzler MJ, Brooks J, Chai A, Van Herle K, Anderson C. Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer. J Clin Invest 1992; 90: 741-748. Posselt AM, Szot GL, Frassetto LA et al. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation 2010; 90: 1595-1601. Koulmanda M, Bhasin M, Hoffman L et al. Curative and beta cell regenerative effects of alpha1-antitrypsin treatment in autoimmune diabetic NOD mice. Proc Natl Acad Sci USA 2008; 105: 16242-16247. Saadoun D, Rosenzwajg M, Joly F et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med 2011; 365: 2067-2077. Burbelo PD, Groot S, Dalakas MC, Iadarola MJ. High definition profiling of autoantibodies to glutamic acid decarboxylases GAD65/GAD67 in stiff-person syndrome. Biochem Biophys Res Commun 2008; 366: 1-7. Liu C, Noorchashm H, Sutter JA et al. B lymphocyte-directed immunotherapy promotes long-term islet allograft survival in nonhuman primates. Nat Med 2007; 13: 1295-1298. Orban T, Farkas K, Jalahej H et al. Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy. J Autoimmun 2009; 34: 408-415. Thomson SA, Sherritt MA, Medveczky J et al. Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination. J Immunol 1998; 160: 1717-1723. Kontzias A, Efthimiou P. The use of Canakinumab, a novel IL-1beta long-acting inhibitor, in refractory adult-onset Still's disease. Semin Arthritis Rheum 2012; 42: 201-205. Plesa G, Zheng L, Medvec A et al. TCR affinity and specificity requirements for human regulatory T-cell function. Blood 2012; 119: 3420-3430. von Herrath MG, Nepom GT. Lost in translation: barriers to implementing clinical immunotherapeutics for autoimmunity. J Exp Med 2005; 202: 1159-1162. Like AA, Rossini AA, Guberski DL, Appel MC, Williams RM. Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Science 1979; 206: 1421-1423. Coppieters KT, Dotta F, Amirian N, et al. Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. J Exp Med. 209: 51-60 Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol 2009; 155: 173-181. Ma L, Qian S, Liang X et al. Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor-kappaB activity. Diabetes 2003; 52: 1976-1985. Mueller DL. Mechanisms maintaining peripheral tolerance. Nat Immunol 2009; 11: 21-27. Steck AK, Armstrong TK, Babu SR, Eisenbarth GS. Type 1 diabetes genetics C. Stepwise or linear decrease in penetrance of type 1 diabetes with lower-risk HLA genotypes over the past 40 years. Diabetes 2011; 60: 1045-1049. Homann D, Holz A, Bot A et al. Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL-4/Stat6 pathway. Immunity 1999; 11: 463-472. Bach JF. Anti-CD3 antibodies for type 1 diabetes: beyond expectations. Lancet 2011; 378: 459-460. Strom A, Kolb H, Martin S et al. Improved preservation of residual beta cell function by atorvastatin in patients with recent onset type 1 diabetes and high CRP levels (DIATOR trial). PLoS One 2012; 7: e33108. 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: 2598-2608. Ichikawa T, Nakayama E, Uenaka A, Monden M, Mori T. Effector cells in allelic H-2 class I-incompatible skin graft rejection. J Exp Med 1987; 166: 982-990. Breit SN, Penny R. The role of alpha 1 protease inhibitor (alpha 1 antitrypsin) in the regulation of immunologic and inflammatory reactions. Aust NZ J Med 1980; 10: 449-453. Arita S, Saul J, Joh S et al. Islet protective effect of pravastatin from nonspecific inflammation in mouse pancreatic islet isografts. Transplant Proc 1996; 28: 924. Marek-Trzonkowska N, Mysliwiec M, Dobyszuk A et al. Administration of CD4+ CD25highCD127- regulatory T cells preserves beta-cell function in type 1 diabetes in children. Diabetes Care 2012; 35: 1817-1820. Kappos L, Comi G, Panitch H et al. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group. Nat Med 2000; 6: 1176-1182. The Diabetes Control and Complications Trial Research Group. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. Ann Intern Med 1998; 128: 517-523. Saudek F, Havrdova T, Boucek P, Karasova L, Novota P, Skibova J. Polyclonal anti-T-cell therapy for type 1 diabetes mellitus of recent onset. Rev Diabet Stud 2004; 1: 80-88. Lozanoska-Ochser B, Barone F, Pitzalis C, Peakman M. Atorvastatin fails to prevent the development of autoimmune diabetes despite inhibit 2012; 61 2007; 148 2009; 88 1998; 160 2010; 10 2010; 53 2010; 59 2012; 366 2000; 6 2002; 110 2002; 51 2010; 17 2011; 60 1997; 46 2011; 61 2004; 4 2009; 155 1999; 163 2008; 105 2012; 18 2011; 12 2004; 1 1992; 10 2003; 52 2009; 11 1992; 90 2009; 52 2011; 208 1996; 28 2013; 56 2004; 173 1999; 11 2002; 346 2008; 359 1998; 128 2009; 361 1996; 2 209 2001; 14 1992; 89 2011; 365 2007; 68 2009; 59 2010; 9 2011; 378 2012; 142 1997; 337 2012; 188 2010; 36 1987; 166 2012 2005; 352 1992; 141 2010; 207 2011 2010 2006; 55 1979; 206 2008; 57 2011; 34 2008; 366 2006; 116 2012; 35 2007; 56 1996; 98 2007; 13 2009; 34 1993; 14 1963; 184 2009; 32 2004; 113 1992; 176 2005; 202 2013; 72 2010; 299 1980; 10 2005; 54 2011; 89 1996; 81 2000; 343 2008; 86 1994; 91 2008; 40 2012; 7 2010; 90 2012; 42 2012; 119 e_1_2_11_70_1 e_1_2_11_93_1 Shah A (e_1_2_11_32_1) 2010; 9 e_1_2_11_55_1 e_1_2_11_78_1 e_1_2_11_36_1 Schneider DA (e_1_2_11_108_1) 2012 e_1_2_11_51_1 e_1_2_11_74_1 e_1_2_11_97_1 e_1_2_11_13_1 e_1_2_11_29_1 e_1_2_11_106_1 e_1_2_11_48_1 e_1_2_11_102_1 e_1_2_11_81_1 e_1_2_11_20_1 e_1_2_11_66_1 e_1_2_11_47_1 e_1_2_11_89_1 e_1_2_11_24_1 e_1_2_11_62_1 e_1_2_11_8_1 e_1_2_11_43_1 e_1_2_11_85_1 Coppieters KT (e_1_2_11_4_1); 209 e_1_2_11_17_1 e_1_2_11_59_1 Thomson SA (e_1_2_11_92_1) 1998; 160 e_1_2_11_50_1 e_1_2_11_77_1 e_1_2_11_58_1 e_1_2_11_35_1 e_1_2_11_73_1 e_1_2_11_12_1 e_1_2_11_54_1 e_1_2_11_96_1 e_1_2_11_103_1 e_1_2_11_28_1 e_1_2_11_5_1 e_1_2_11_61_1 e_1_2_11_80_1 e_1_2_11_46_1 e_1_2_11_69_1 e_1_2_11_88_1 e_1_2_11_107_1 Buyukgebiz A (e_1_2_11_19_1) 2001; 14 e_1_2_11_9_1 e_1_2_11_23_1 e_1_2_11_42_1 e_1_2_11_65_1 e_1_2_11_84_1 e_1_2_11_16_1 e_1_2_11_39_1 Elias D (e_1_2_11_60_1) 1997; 46 e_1_2_11_72_1 e_1_2_11_91_1 e_1_2_11_30_1 e_1_2_11_57_1 e_1_2_11_99_1 e_1_2_11_34_1 e_1_2_11_53_1 e_1_2_11_76_1 e_1_2_11_95_1 e_1_2_11_11_1 e_1_2_11_6_1 e_1_2_11_104_1 e_1_2_11_27_1 e_1_2_11_2_1 e_1_2_11_100_1 Barlow AK (e_1_2_11_31_1) 1992; 141 e_1_2_11_83_1 e_1_2_11_45_1 e_1_2_11_68_1 e_1_2_11_41_1 e_1_2_11_87_1 e_1_2_11_22_1 Arita S (e_1_2_11_64_1) 1996; 28 e_1_2_11_15_1 e_1_2_11_38_1 e_1_2_11_94_1 e_1_2_11_90_1 e_1_2_11_10_1 e_1_2_11_56_1 e_1_2_11_79_1 e_1_2_11_14_1 e_1_2_11_52_1 e_1_2_11_98_1 e_1_2_11_33_1 e_1_2_11_75_1 e_1_2_11_7_1 e_1_2_11_105_1 e_1_2_11_26_1 e_1_2_11_3_1 e_1_2_11_49_1 e_1_2_11_101_1 Herman AE (e_1_2_11_71_1) 1999; 163 e_1_2_11_82_1 e_1_2_11_21_1 e_1_2_11_44_1 e_1_2_11_67_1 e_1_2_11_25_1 e_1_2_11_40_1 e_1_2_11_63_1 e_1_2_11_86_1 e_1_2_11_18_1 e_1_2_11_37_1
References_xml	– reference: Strom A, Kolb H, Martin S et al. Improved preservation of residual beta cell function by atorvastatin in patients with recent onset type 1 diabetes and high CRP levels (DIATOR trial). PLoS One 2012; 7: e33108. – reference: 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: 1909-1920. – reference: Michels AW, Nakayama M. The anti-insulin trimolecular complex in type 1 diabetes. Curr Opin Endocrinol Diabetes Obes 2010; 17: 329-334. – reference: Burbelo PD, Groot S, Dalakas MC, Iadarola MJ. High definition profiling of autoantibodies to glutamic acid decarboxylases GAD65/GAD67 in stiff-person syndrome. Biochem Biophys Res Commun 2008; 366: 1-7. – reference: Jonker M, Ringers J, Kuhn EM, 't Hart B, Foulkes R. Treatment with anti-MHC-class-II antibody postpones kidney allograft rejection in primates but increases the risk of CMV activation. Am J Transplant 2004; 4: 1756-1761. – reference: Steck AK, Armstrong TK, Babu SR, Eisenbarth GS. Type 1 diabetes genetics C. Stepwise or linear decrease in penetrance of type 1 diabetes with lower-risk HLA genotypes over the past 40 years. Diabetes 2011; 60: 1045-1049. – reference: Saadoun D, Rosenzwajg M, Joly F et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med 2011; 365: 2067-2077. – reference: Liu C, Noorchashm H, Sutter JA et al. B lymphocyte-directed immunotherapy promotes long-term islet allograft survival in nonhuman primates. Nat Med 2007; 13: 1295-1298. – reference: Brusko TM, Wasserfall CH, Clare-Salzler MJ, Schatz DA, Atkinson MA. Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes. Diabetes 2005; 54: 1407-1414. – reference: 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: 1692-1698. – reference: Marek-Trzonkowska N, Mysliwiec M, Dobyszuk A et al. Administration of CD4+ CD25highCD127- regulatory T cells preserves beta-cell function in type 1 diabetes in children. Diabetes Care 2012; 35: 1817-1820. – reference: Plesa G, Zheng L, Medvec A et al. TCR affinity and specificity requirements for human regulatory T-cell function. Blood 2012; 119: 3420-3430. – reference: Schneider DA, Sarikonda G, von Herrath MG. Combination therapy with InsB9-23 peptide immunization and CTLA4-IgG does not reverse diabetes in NOD mice. Clin Immunol 2012; 142: 402-403. – reference: 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: 412-419. – reference: Marchand KC, Arany EJ, Hill DJ. Effects of atorvastatin on the regeneration of pancreatic {beta}-cells after streptozotocin treatment in the neonatal rodent. Am J Physiol Endocrinol Metab 2010; 299: E92-E100. – reference: Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. Annu Rev Immunol 1992; 10: 153-187. – reference: Arita S, Saul J, Joh S et al. Islet protective effect of pravastatin from nonspecific inflammation in mouse pancreatic islet isografts. Transplant Proc 1996; 28: 924. – reference: Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree TI. Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 2005; 54: 92-99. – reference: Yu L, Rewers M, Gianani R et al. Antiislet autoantibodies usually develop sequentially rather than simultaneously. J Clin Endocrinol Metab 1996; 81: 4264-4267. – reference: Homann D, Holz A, Bot A et al. Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL-4/Stat6 pathway. Immunity 1999; 11: 463-472. – reference: 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: 390-401. – reference: Ma L, Qian S, Liang X et al. Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor-kappaB activity. Diabetes 2003; 52: 1976-1985. – reference: Mueller DL. Mechanisms maintaining peripheral tolerance. Nat Immunol 2009; 11: 21-27. – reference: The Diabetes Control and Complications Trial Research Group. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. Ann Intern Med 1998; 128: 517-523. – reference: Winthrop K, Baxter R, Liu L et al. Mycobacterial diseases and antitumour necrosis factor therapy in USA. Ann Rheum Dis 2013; 72: 37-42. – reference: Zanin-Zhorov A, Cahalon L, Tal G, Margalit R, Lider O, Cohen IR. Heat shock protein 60 enhances CD4+ CD25+ regulatory T cell function via innate TLR2 signaling. J Clin Invest 2006; 116: 2022-2032. – reference: Clemente-Casares X, Tsai S, Yang Y, Santamaria P. Peptide-MHC-based nanovaccines for the treatment of autoimmunity: a "one size fits all" approach? J Mol Med (Berl) 2011; 89: 733-742. – reference: Dromey JA, Lee BH, Yu H et al. Generation and expansion of regulatory human CD4(+) T-cell clones specific for pancreatic islet autoantigens. J Autoimmun 2010; 36: 47-55. – reference: Maki T, Ichikawa T, Blanco R, Porter J. Long-term abrogation of autoimmune diabetes in nonobese diabetic mice by immunotherapy with anti-lymphocyte serum. Proc Natl Acad Sci USA 1992; 89: 3434-3438. – reference: Suarez-Pinzon WL, Cembrowski GS, Rabinovitch A. Combination therapy with a dipeptidyl peptidase-4 inhibitor and a proton pump inhibitor restores normoglycaemia in non-obese diabetic mice. Diabetologia 2009; 52: 1680-1682. – reference: Bresson D, Togher L, Rodrigo E et al. Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. J Clin Invest 2006; 116: 1371-1381. – reference: Koulmanda M, Bhasin M, Hoffman L et al. Curative and beta cell regenerative effects of alpha1-antitrypsin treatment in autoimmune diabetic NOD mice. Proc Natl Acad Sci USA 2008; 105: 16242-16247. – reference: Shapiro AM, Lakey JR, Ryan EA et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343: 230-238. – reference: Coppieters KT, Dotta F, Amirian N, et al. Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. J Exp Med. 209: 51-60 – reference: Liu E, Moriyama H, Abiru N et al. Anti-peptide autoantibodies and fatal anaphylaxis in NOD mice in response to insulin self-peptides B:9-23 and B:13-23. J Clin Invest 2002; 110: 1021-1027. – reference: Breit SN, Penny R. The role of alpha 1 protease inhibitor (alpha 1 antitrypsin) in the regulation of immunologic and inflammatory reactions. Aust NZ J Med 1980; 10: 449-453. – reference: Mastrandrea L, Yu J, Behrens T et al. Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, double-blind study. Diabetes Care 2009; 32: 1244-1249. – reference: Bach JF. Anti-CD3 antibodies for type 1 diabetes: beyond expectations. Lancet 2011; 378: 459-460. – reference: 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: 1348-1353. – reference: Walter M, Philotheou A, Bonnici F, Ziegler AG, Jimenez R, Group NBIS. No effect of the altered peptide ligand NBI-6024 on beta-cell residual function and insulin needs in new-onset type 1 diabetes. Diabetes Care 2009; 32: 2036-2040. – reference: Thomson SA, Sherritt MA, Medveczky J et al. Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination. J Immunol 1998; 160: 1717-1723. – reference: In't Veld P, Lievens D, De Grijse J et al. Screening for insulitis in adult autoantibody-positive organ donors. Diabetes 2007; 56: 2400-2404. – reference: Rabinovitch A, Suarez-Pinzon WL, Shapiro AM, Rajotte RV, Power R. Combination therapy with sirolimus and interleukin-2 prevents spontaneous and recurrent autoimmune diabetes in NOD mice. Diabetes 2002; 51: 638-645. – reference: Schneider DA, Boettler T, von-Herrath MG. Novel approach to test for immune protecting properties of semipermeable membranes in pancreatic islet transplantation. Scientific Sessions of the American Diabetes Association. Philadelphia, 2012. – reference: Clare-Salzler MJ, Brooks J, Chai A, Van Herle K, Anderson C. Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer. J Clin Invest 1992; 90: 741-748. – reference: Yi Z, Diz R, Martin AJ et al. Long-term remission of diabetes in NOD mice is induced by nondepleting anti-CD4 and anti-CD8 antibodies. Diabetes 2012; 61: 2871-2880. – reference: Barlow AK, Like AA. Anti-CD2 monoclonal antibodies prevent spontaneous and adoptive transfer of diabetes in the BB/Wor rat. Am J Pathol 1992; 141: 1043-1051. – reference: Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med 2009; 361: 2143-2152. – reference: Keenan HA, Sun JK, Levine J et al. Residual insulin production and pancreatic ss-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes 2010; 59: 2846-2853. – reference: 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: 1871-1878. – reference: Herman AE, Tisch RM, Patel SD et al. Determination of glutamic acid decarboxylase 65 peptides presented by the type I diabetes-associated HLA-DQ8 class II molecule identifies an immunogenic peptide motif. J Immunol 1999; 163: 6275-6282. – reference: Linsley PS, Greene JL, Tan P et al. Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J Exp Med 1992; 176: 1595-1604. – reference: Elias D, Meilin A, Ablamunits V et al. Hsp60 peptide therapy of NOD mouse diabetes induces a Th2 cytokine burst and downregulates autoimmunity to various beta-cell antigens. Diabetes 1997; 46: 758-764. – reference: Issa F, Hester J, Goto R, Nadig SN, Goodacre TE, Wood K. Ex vivo-expanded human regulatory T cells prevent the rejection of skin allografts in a humanized mouse model. Transplantation 2010; 90: 1321-1327. – reference: Tarantal AF, Lee CC, Itkin-Ansari P. Real-time bioluminescence imaging of macroencapsulated fibroblasts reveals allograft protection in rhesus monkeys (Macaca mulatta). Transplantation 2009; 88: 38-41. – reference: Posselt AM, Szot GL, Frassetto LA et al. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation 2010; 90: 1595-1601. – reference: Kontzias A, Efthimiou P. The use of Canakinumab, a novel IL-1beta long-acting inhibitor, in refractory adult-onset Still's disease. Semin Arthritis Rheum 2012; 42: 201-205. – reference: Lozanoska-Ochser B, Barone F, Pitzalis C, Peakman M. Atorvastatin fails to prevent the development of autoimmune diabetes despite inhibition of pathogenic beta-cell-specific CD8 T-cells. Diabetes 2006; 55: 1004-1010. – reference: Ferrannini E, Mari A, Nofrate V, Sosenko JM, Skyler JS, Group DPTS. Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and mode of onset. Diabetes 2009; 59: 679-685. – reference: Judkowski V, Rodriguez E, Pinilla C et al. Peptide specific amelioration of T cell mediated pathogenesis in murine type 1 diabetes. Clin Immunol 2004; 113: 29-37. – reference: Bielekova B, Goodwin B, Richert N et al. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand. Nat Med 2000; 6: 1167-1175. – reference: Like AA, Rossini AA, Guberski DL, Appel MC, Williams RM. Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Science 1979; 206: 1421-1423. – reference: Sumpter KM, Adhikari S, Grishman EK, White PC. Preliminary studies related to anti-interleukin-1beta therapy in children with newly diagnosed type 1 diabetes. Pediatr Diabetes 2011; 12: 656-667. – reference: 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: 5136-5144. – reference: Erlich H, Valdes AM, Noble J et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes 2008; 57: 1084-1092. – reference: Ablamunits V, Henegariu O, Hansen JB et al. Synergistic reversal of type 1 diabetes in NOD mice with anti-CD3 and interleukin-1 blockade: evidence of improved immune regulation. Diabetes 2011; 61: 145-154. – reference: Saudek F, Havrdova T, Boucek P, Karasova L, Novota P, Skibova J. Polyclonal anti-T-cell therapy for type 1 diabetes mellitus of recent onset. Rev Diabet Stud 2004; 1: 80-88. – reference: Daniel C, Weigmann B, Bronson R, von Boehmer H. Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope. J Exp Med 2011; 208: 1501-1510. – reference: Buyukgebiz A, Cemeroglu AP, Bober E, Mohn A, Chiarelli F. Factors influencing remission phase in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2001; 14: 1585-1596. – reference: Buzzetti R, Cernea S, Petrone A et al. C-peptide response and HLA genotypes in subjects with recent-onset type 1 diabetes after immunotherapy with DiaPep277: an exploratory study. Diabetes 2011; 60: 3067-3072. – reference: Liddy N, Bossi G, Adams KJ et al. Monoclonal TCR-redirected tumor cell killing. Nat Med 2012; 18: 980-987. – reference: Lehmann PV, Sercarz EE, Forsthuber T, Dayan CM, Gammon G. Determinant spreading and the dynamics of the autoimmune T-cell repertoire. Immunol Today 1993; 14: 203-208. – reference: Nagler W, Taylor H. Diabetic coma with acute inflammation of Islets of Langerhans. JAMA 1963; 184: 723-725. – reference: Gianani R, Campbell-Thompson M, Sarkar SA et al. Dimorphic histopathology of long-standing childhood-onset diabetes. Diabetologia 2010; 53: 690-698. – reference: Suarez-Pinzon WL, Power RF, Yan Y, Wasserfall C, Atkinson M, Rabinovitch A. Combination therapy with glucagon-like peptide-1 and gastrin restores normoglycemia in diabetic NOD mice. Diabetes 2008; 57: 3281-3288. – reference: Ichikawa T, Nakayama E, Uenaka A, Monden M, Mori T. Effector cells in allelic H-2 class I-incompatible skin graft rejection. J Exp Med 1987; 166: 982-990. – reference: Orban T, Farkas K, Jalahej H et al. Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy. J Autoimmun 2009; 34: 408-415. – reference: von Herrath MG, Nepom GT. Lost in translation: barriers to implementing clinical immunotherapeutics for autoimmunity. J Exp Med 2005; 202: 1159-1162. – reference: Sorenby AK, Kumagai-Braesch M, Sharma A, Hultenby KR, Wernerson AM, Tibell AB. Preimplantation of an immunoprotective device can lower the curative dose of islets to that of free islet transplantation: studies in a rodent model. Transplantation 2008; 86: 364-366. – reference: Shah A, O'Neill J, Feldman SR. Treatment of moderate-to-severe psoriasis with alefacept for up to one year: a case series. J Drugs Dermatol 2010; 9: 1491-1494. – reference: Hernandez A, Burger M, Blomberg BB et al. Inhibition of NF-kappa B during human dendritic cell differentiation generates anergy and regulatory T-cell activity for one but not two human leukocyte antigen DR mismatches. Hum Immunol 2007; 68: 715-729. – reference: Fallahi-Sichani M, Flynn JL, Linderman JJ, Kirschner DE. Differential risk of tuberculosis reactivation among anti-TNF therapies is due to drug binding kinetics and permeability. J Immunol 2012; 188: 3169-3178. – reference: Pileggi A, Molano RD, Song S et al. Alpha-1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts. Transplant Proc 2008; 40: 457-458. – reference: Epstein WV. Treatment of rheumatoid arthritis with a tumor necrosis factor receptor-Fc fusion protein. N Engl J Med 1997; 337: 1559-1560; author reply 1560-1551. – reference: Long SA, Rieck M, Sanda S et al. Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs beta-cell function. Diabetes 2012; 61: 2340-2348. – reference: Kappos L, Comi G, Panitch H et al. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group. Nat Med 2000; 6: 1176-1182. – reference: Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol 2009; 155: 173-181. – reference: 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: 123-127. – reference: Machen J, Harnaha J, Lakomy R, Styche A, Trucco M, Giannoukakis N. Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J Immunol 2004; 173: 4331-4341. – reference: Fourlanos S, Perry C, Gellert SA et al. Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes. Diabetes 2011; 60: 1237-1245. – reference: von Herrath MG, Dyrberg T, Oldstone MB. Oral insulin treatment suppresses virus-induced antigen-specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice. J Clin Invest 1996; 98: 1324-1331. – reference: Vehik K, Cuthbertson D, Ruhlig H et al. Long-term outcome of individuals treated with oral insulin: diabetes prevention trial-type 1 (DPT-1) oral insulin trial. Diabetes Care 2011; 34: 1585-1590. – reference: Oo YH, Mutimer D, Adams DH. Low-dose interleukin-2 and HCV-induced vasculitis. N Engl J Med 2012; 366: 1353-1354; author reply 1354. – reference: 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: 2598-2608. – reference: Posselt AM, Bellin MD, Tavakol M et al. Islet transplantation in type 1 diabetics using an immunosuppressive protocol based on the anti-LFA-1 antibody efalizumab. Am J Transplant 2010; 10: 1870-1880. – year: 2011 – volume: 12 start-page: 656 year: 2011 end-page: 667 article-title: Preliminary studies related to anti‐interleukin‐1beta therapy in children with newly diagnosed type 1 diabetes publication-title: Pediatr Diabetes – volume: 81 start-page: 4264 year: 1996 end-page: 4267 article-title: Antiislet autoantibodies usually develop sequentially rather than simultaneously publication-title: J Clin Endocrinol Metab – volume: 365 start-page: 2067 year: 2011 end-page: 2077 article-title: Regulatory T‐cell responses to low‐dose interleukin‐2 in HCV‐induced vasculitis publication-title: N Engl J Med – volume: 166 start-page: 982 year: 1987 end-page: 990 article-title: Effector cells in allelic H‐2 class I‐incompatible skin graft rejection publication-title: J Exp Med – volume: 52 start-page: 1680 year: 2009 end-page: 1682 article-title: Combination therapy with a dipeptidyl peptidase‐4 inhibitor and a proton pump inhibitor restores normoglycaemia in non‐obese diabetic mice publication-title: Diabetologia – volume: 7 start-page: e33108 year: 2012 article-title: Improved preservation of residual beta cell function by atorvastatin in patients with recent onset type 1 diabetes and high CRP levels (DIATOR trial) publication-title: PLoS One – volume: 90 start-page: 741 year: 1992 end-page: 748 article-title: Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer publication-title: J Clin Invest – volume: 116 start-page: 1371 year: 2006 end-page: 1381 article-title: Anti‐CD3 and nasal proinsulin combination therapy enhances remission from recent‐onset autoimmune diabetes by inducing Tregs publication-title: J Clin Invest – volume: 116 start-page: 2022 year: 2006 end-page: 2032 article-title: Heat shock protein 60 enhances CD4+ CD25+ regulatory T cell function via innate TLR2 signaling publication-title: J Clin Invest – volume: 378 start-page: 412 year: 2011 end-page: 419 article-title: Co‐stimulation modulation with abatacept in patients with recent‐onset type 1 diabetes: a randomised, double‐blind, placebo‐controlled trial publication-title: Lancet – volume: 346 start-page: 1692 year: 2002 end-page: 1698 article-title: Anti‐CD3 monoclonal antibody in new‐onset type 1 diabetes mellitus publication-title: N Engl J Med – volume: 6 start-page: 1167 year: 2000 end-page: 1175 article-title: Encephalitogenic potential of the myelin basic protein peptide (amino acids 83–99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand publication-title: Nat Med – volume: 34 start-page: 1585 year: 2011 end-page: 1590 article-title: Long‐term outcome of individuals treated with oral insulin: diabetes prevention trial‐type 1 (DPT‐1) oral insulin trial publication-title: Diabetes Care – volume: 18 start-page: 980 year: 2012 end-page: 987 article-title: Monoclonal TCR‐redirected tumor cell killing publication-title: Nat Med – volume: 148 start-page: 5136 year: 2007 end-page: 5144 article-title: Exendin‐4 improves reversal of diabetes in NOD mice treated with anti‐CD3 monoclonal antibody by enhancing recovery of beta‐cells publication-title: Endocrinology – volume: 88 start-page: 38 year: 2009 end-page: 41 article-title: Real‐time bioluminescence imaging of macroencapsulated fibroblasts reveals allograft protection in rhesus monkeys (Macaca mulatta) publication-title: Transplantation – volume: 68 start-page: 715 year: 2007 end-page: 729 article-title: Inhibition of NF‐kappa B during human dendritic cell differentiation generates anergy and regulatory T‐cell activity for one but not two human leukocyte antigen DR mismatches publication-title: Hum Immunol – volume: 105 start-page: 16242 year: 2008 end-page: 16247 article-title: Curative and beta cell regenerative effects of alpha1‐antitrypsin treatment in autoimmune diabetic NOD mice publication-title: Proc Natl Acad Sci USA – volume: 60 start-page: 3067 year: 2011 end-page: 3072 article-title: C‐peptide response and HLA genotypes in subjects with recent‐onset type 1 diabetes after immunotherapy with DiaPep277: an exploratory study publication-title: Diabetes – volume: 141 start-page: 1043 year: 1992 end-page: 1051 article-title: Anti‐CD2 monoclonal antibodies prevent spontaneous and adoptive transfer of diabetes in the BB/Wor rat publication-title: Am J Pathol – volume: 90 start-page: 1321 year: 2010 end-page: 1327 article-title: Ex vivo‐expanded human regulatory T cells prevent the rejection of skin allografts in a humanized mouse model publication-title: Transplantation – volume: 119 start-page: 3420 year: 2012 end-page: 3430 article-title: TCR affinity and specificity requirements for human regulatory T‐cell function publication-title: Blood – volume: 35 start-page: 1817 year: 2012 end-page: 1820 article-title: Administration of CD4+ CD25highCD127‐ regulatory T cells preserves beta‐cell function in type 1 diabetes in children publication-title: Diabetes Care – volume: 184 start-page: 723 year: 1963 end-page: 725 article-title: Diabetic coma with acute inflammation of Islets of Langerhans publication-title: JAMA – volume: 61 start-page: 2340 year: 2012 end-page: 2348 article-title: Rapamycin/IL‐2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs beta‐cell function publication-title: Diabetes – volume: 61 start-page: 145 year: 2011 end-page: 154 article-title: Synergistic reversal of type 1 diabetes in NOD mice with anti‐CD3 and interleukin‐1 blockade: evidence of improved immune regulation publication-title: Diabetes – volume: 128 start-page: 517 year: 1998 end-page: 523 article-title: Effect of intensive therapy on residual beta‐cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial publication-title: Ann Intern Med – volume: 113 start-page: 29 year: 2004 end-page: 37 article-title: Peptide specific amelioration of T cell mediated pathogenesis in murine type 1 diabetes publication-title: Clin Immunol – year: 2010 – volume: 10 start-page: 449 year: 1980 end-page: 453 article-title: The role of alpha 1 protease inhibitor (alpha 1 antitrypsin) in the regulation of immunologic and inflammatory reactions publication-title: Aust NZ J Med – volume: 57 start-page: 1084 year: 2008 end-page: 1092 article-title: HLA DR‐DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families publication-title: Diabetes – volume: 2 start-page: 1348 year: 1996 end-page: 1353 article-title: Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes‐prone mice publication-title: Nat Med – volume: 17 start-page: 329 year: 2010 end-page: 334 article-title: The anti‐insulin trimolecular complex in type 1 diabetes publication-title: Curr Opin Endocrinol Diabetes Obes – volume: 60 start-page: 1237 year: 2011 end-page: 1245 article-title: Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes publication-title: Diabetes – volume: 91 start-page: 123 year: 1994 end-page: 127 article-title: Anti‐CD3 antibody induces long‐term remission of overt autoimmunity in nonobese diabetic mice publication-title: Proc Natl Acad Sci USA – volume: 54 start-page: 92 year: 2005 end-page: 99 article-title: Defective suppressor function in CD4(+)CD25(+) T‐cells from patients with type 1 diabetes publication-title: Diabetes – volume: 155 start-page: 173 year: 2009 end-page: 181 article-title: Analysis of islet inflammation in human type 1 diabetes publication-title: Clin Exp Immunol – volume: 32 start-page: 2036 year: 2009 end-page: 2040 article-title: No effect of the altered peptide ligand NBI‐6024 on beta‐cell residual function and insulin needs in new‐onset type 1 diabetes publication-title: Diabetes Care – volume: 188 start-page: 3169 year: 2012 end-page: 3178 article-title: Differential risk of tuberculosis reactivation among anti‐TNF therapies is due to drug binding kinetics and permeability publication-title: J Immunol – volume: 86 start-page: 364 year: 2008 end-page: 366 article-title: Preimplantation of an immunoprotective device can lower the curative dose of islets to that of free islet transplantation: studies in a rodent model publication-title: Transplantation – volume: 13 start-page: 1295 year: 2007 end-page: 1298 article-title: B lymphocyte‐directed immunotherapy promotes long‐term islet allograft survival in nonhuman primates publication-title: Nat Med – volume: 32 start-page: 1244 year: 2009 end-page: 1249 article-title: Etanercept treatment in children with new‐onset type 1 diabetes: pilot randomized, placebo‐controlled, double‐blind study publication-title: Diabetes Care – volume: 10 start-page: 153 year: 1992 end-page: 187 article-title: Immunological aspects of demyelinating diseases publication-title: Annu Rev Immunol – volume: 1 start-page: 80 year: 2004 end-page: 88 article-title: Polyclonal anti‐T‐cell therapy for type 1 diabetes mellitus of recent onset publication-title: Rev Diabet Stud – volume: 359 start-page: 1909 year: 2008 end-page: 1920 article-title: GAD treatment and insulin secretion in recent‐onset type 1 diabetes publication-title: N Engl J Med – volume: 361 start-page: 2143 year: 2009 end-page: 2152 article-title: Rituximab, B‐lymphocyte depletion, and preservation of beta‐cell function publication-title: N Engl J Med – volume: 202 start-page: 1159 year: 2005 end-page: 1162 article-title: Lost in translation: barriers to implementing clinical immunotherapeutics for autoimmunity publication-title: J Exp Med – volume: 6 start-page: 1176 year: 2000 end-page: 1182 article-title: Induction of a non‐encephalitogenic type 2 T helper‐cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo‐controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group publication-title: Nat Med – volume: 160 start-page: 1717 year: 1998 end-page: 1723 article-title: Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination publication-title: J Immunol – volume: 11 start-page: 463 year: 1999 end-page: 472 article-title: Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL‐4/Stat6 pathway publication-title: Immunity – volume: 337 start-page: 1559 year: 1997 end-page: 1560 article-title: Treatment of rheumatoid arthritis with a tumor necrosis factor receptor‐Fc fusion protein publication-title: N Engl J Med – volume: 72 start-page: 37 year: 2013 end-page: 42 article-title: Mycobacterial diseases and antitumour necrosis factor therapy in USA publication-title: Ann Rheum Dis – volume: 14 start-page: 203 year: 1993 end-page: 208 article-title: Determinant spreading and the dynamics of the autoimmune T‐cell repertoire publication-title: Immunol Today – volume: 14 start-page: 1585 year: 2001 end-page: 1596 article-title: Factors influencing remission phase in children with type 1 diabetes mellitus publication-title: J Pediatr Endocrinol Metab – volume: 173 start-page: 4331 year: 2004 end-page: 4341 article-title: Antisense oligonucleotides down‐regulating costimulation confer diabetes‐preventive properties to nonobese diabetic mouse dendritic cells publication-title: J Immunol – volume: 34 start-page: 408 year: 2009 end-page: 415 article-title: Autoantigen‐specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B‐chain immunotherapy publication-title: J Autoimmun – volume: 28 start-page: 924 year: 1996 article-title: Islet protective effect of pravastatin from nonspecific inflammation in mouse pancreatic islet isografts publication-title: Transplant Proc – volume: 98 start-page: 1324 year: 1996 end-page: 1331 article-title: Oral insulin treatment suppresses virus‐induced antigen‐specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice publication-title: J Clin Invest – volume: 366 start-page: 1 year: 2008 end-page: 7 article-title: High definition profiling of autoantibodies to glutamic acid decarboxylases GAD65/GAD67 in stiff‐person syndrome publication-title: Biochem Biophys Res Commun – volume: 51 start-page: 638 year: 2002 end-page: 645 article-title: Combination therapy with sirolimus and interleukin‐2 prevents spontaneous and recurrent autoimmune diabetes in NOD mice publication-title: Diabetes – volume: 206 start-page: 1421 year: 1979 end-page: 1423 article-title: Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes publication-title: Science – volume: 4 start-page: 390 year: 2004 end-page: 401 article-title: Transplantation of cultured islets from two‐layer preserved pancreases in type 1 diabetes with anti‐CD3 antibody publication-title: Am J Transplant – volume: 208 start-page: 1501 year: 2011 end-page: 1510 article-title: Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope publication-title: J Exp Med – volume: 110 start-page: 1021 year: 2002 end-page: 1027 article-title: Anti‐peptide autoantibodies and fatal anaphylaxis in NOD mice in response to insulin self‐peptides B:9‐23 and B:13‐23 publication-title: J Clin Invest – volume: 46 start-page: 758 year: 1997 end-page: 764 article-title: Hsp60 peptide therapy of NOD mouse diabetes induces a Th2 cytokine burst and downregulates autoimmunity to various beta‐cell antigens publication-title: Diabetes – volume: 56 start-page: 391 year: 2013 end-page: 400 – volume: 366 start-page: 1353 year: 2012 end-page: 1354 article-title: Low‐dose interleukin‐2 and HCV‐induced vasculitis publication-title: N Engl J Med – volume: 352 start-page: 2598 year: 2005 end-page: 2608 article-title: Insulin needs after CD3‐antibody therapy in new‐onset type 1 diabetes publication-title: N Engl J Med – volume: 4 start-page: 1756 year: 2004 end-page: 1761 article-title: Treatment with anti‐MHC‐class‐II antibody postpones kidney allograft rejection in primates but increases the risk of CMV activation publication-title: Am J Transplant – volume: 209 start-page: 51 end-page: 60 article-title: Demonstration of islet‐autoreactive CD8 T cells in insulitic lesions from recent onset and long‐term type 1 diabetes patients publication-title: J Exp Med – volume: 9 start-page: 1491 year: 2010 end-page: 1494 article-title: Treatment of moderate‐to‐severe psoriasis with alefacept for up to one year: a case series publication-title: J Drugs Dermatol – volume: 40 start-page: 457 year: 2008 end-page: 458 article-title: Alpha‐1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts publication-title: Transplant Proc – volume: 56 start-page: 2400 year: 2007 end-page: 2404 article-title: Screening for insulitis in adult autoantibody‐positive organ donors publication-title: Diabetes – volume: 60 start-page: 1045 year: 2011 end-page: 1049 article-title: Type 1 diabetes genetics C. Stepwise or linear decrease in penetrance of type 1 diabetes with lower‐risk HLA genotypes over the past 40 years publication-title: Diabetes – volume: 61 start-page: 2871 year: 2012 end-page: 2880 article-title: Long‐term remission of diabetes in NOD mice is induced by nondepleting anti‐CD4 and anti‐CD8 antibodies publication-title: Diabetes – year: 2012 – volume: 59 start-page: 2846 year: 2010 end-page: 2853 article-title: Residual insulin production and pancreatic ss‐cell turnover after 50 years of diabetes: Joslin Medalist Study publication-title: Diabetes – volume: 55 start-page: 1004 year: 2006 end-page: 1010 article-title: Atorvastatin fails to prevent the development of autoimmune diabetes despite inhibition of pathogenic beta‐cell‐specific CD8 T‐cells publication-title: Diabetes – volume: 42 start-page: 201 year: 2012 end-page: 205 article-title: The use of Canakinumab, a novel IL‐1beta long‐acting inhibitor, in refractory adult‐onset Still's disease publication-title: Semin Arthritis Rheum – volume: 59 start-page: 679 year: 2009 end-page: 685 article-title: Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and mode of onset publication-title: Diabetes – volume: 378 start-page: 459 year: 2011 end-page: 460 article-title: Anti‐CD3 antibodies for type 1 diabetes: beyond expectations publication-title: Lancet – volume: 343 start-page: 230 year: 2000 end-page: 238 article-title: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid‐free immunosuppressive regimen publication-title: N Engl J Med – volume: 53 start-page: 690 year: 2010 end-page: 698 article-title: Dimorphic histopathology of long‐standing childhood‐onset diabetes publication-title: Diabetologia – volume: 90 start-page: 1595 year: 2010 end-page: 1601 article-title: Islet transplantation in type 1 diabetic patients using calcineurin inhibitor‐free immunosuppressive protocols based on T‐cell adhesion or costimulation blockade publication-title: Transplantation – volume: 11 start-page: 21 year: 2009 end-page: 27 article-title: Mechanisms maintaining peripheral tolerance publication-title: Nat Immunol – volume: 52 start-page: 1976 year: 2003 end-page: 1985 article-title: Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor‐kappaB activity publication-title: Diabetes – volume: 89 start-page: 733 year: 2011 end-page: 742 article-title: Peptide‐MHC‐based nanovaccines for the treatment of autoimmunity: a “one size fits all” approach? publication-title: J Mol Med (Berl) – volume: 54 start-page: 1407 year: 2005 end-page: 1414 article-title: Functional defects and the influence of age on the frequency of CD4+ CD25+ T‐cells in type 1 diabetes publication-title: Diabetes – volume: 57 start-page: 3281 year: 2008 end-page: 3288 article-title: Combination therapy with glucagon‐like peptide‐1 and gastrin restores normoglycemia in diabetic NOD mice publication-title: Diabetes – volume: 36 start-page: 47 year: 2010 end-page: 55 article-title: Generation and expansion of regulatory human CD4(+) T‐cell clones specific for pancreatic islet autoantigens publication-title: J Autoimmun – volume: 10 start-page: 1870 year: 2010 end-page: 1880 article-title: Islet transplantation in type 1 diabetics using an immunosuppressive protocol based on the anti‐LFA‐1 antibody efalizumab publication-title: Am J Transplant – year: 2012 publication-title: Scientific Sessions of the American Diabetes Association – volume: 163 start-page: 6275 year: 1999 end-page: 6282 article-title: Determination of glutamic acid decarboxylase 65 peptides presented by the type I diabetes‐associated HLA‐DQ8 class II molecule identifies an immunogenic peptide motif publication-title: J Immunol – volume: 299 start-page: E92 year: 2010 end-page: E100 article-title: Effects of atorvastatin on the regeneration of pancreatic {beta}‐cells after streptozotocin treatment in the neonatal rodent publication-title: Am J Physiol Endocrinol Metab – volume: 176 start-page: 1595 year: 1992 end-page: 1604 article-title: Coexpression and functional cooperation of CTLA‐4 and CD28 on activated T lymphocytes publication-title: J Exp Med – volume: 142 start-page: 402 year: 2012 end-page: 403 article-title: Combination therapy with InsB9‐23 peptide immunization and CTLA4‐IgG does not reverse diabetes in NOD mice publication-title: Clin Immunol – volume: 89 start-page: 3434 year: 1992 end-page: 3438 article-title: Long‐term abrogation of autoimmune diabetes in nonobese diabetic mice by immunotherapy with anti‐lymphocyte serum publication-title: Proc Natl Acad Sci USA – volume: 207 start-page: 1871 year: 2010 end-page: 1878 article-title: IL‐2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells publication-title: J Exp Med – ident: e_1_2_11_22_1 doi: 10.1038/80516 – ident: e_1_2_11_39_1 doi: 10.1056/NEJMc1200978 – ident: e_1_2_11_75_1 doi: 10.2337/db10-1360 – ident: e_1_2_11_45_1 doi: 10.1001/jama.1963.73700220012020c – ident: e_1_2_11_57_1 doi: 10.4049/jimmunol.1103298 – ident: e_1_2_11_80_1 doi: 10.1210/en.2007-0358 – ident: e_1_2_11_2_1 doi: 10.2337/db07-1331 – ident: e_1_2_11_55_1 doi: 10.1056/NEJM199711203372118 – ident: e_1_2_11_17_1 doi: 10.1056/NEJMoa043980 – ident: e_1_2_11_54_1 – ident: e_1_2_11_15_1 doi: 10.1016/j.clim.2004.03.007 – ident: e_1_2_11_38_1 doi: 10.1084/jem.20100209 – ident: e_1_2_11_56_1 doi: 10.2337/dc09-0054 – ident: e_1_2_11_88_1 doi: 10.4049/jimmunol.173.7.4331 – ident: e_1_2_11_103_1 doi: 10.1097/TP.0b013e3181fe1377 – ident: e_1_2_11_14_1 doi: 10.2337/db10-0676 – ident: e_1_2_11_89_1 doi: 10.1084/jem.20110574 – ident: e_1_2_11_69_1 doi: 10.1016/j.jaut.2010.10.005 – ident: e_1_2_11_6_1 doi: 10.2337/diabetes.54.1.92 – ident: e_1_2_11_98_1 doi: 10.1007/s00109-011-0757-z – ident: e_1_2_11_18_1 doi: 10.7326/0003-4819-128-7-199804010-00001 – volume: 209 start-page: 51 ident: e_1_2_11_4_1 article-title: Demonstration of islet‐autoreactive CD8 T cells in insulitic lesions from recent onset and long‐term type 1 diabetes patients publication-title: J Exp Med doi: 10.1084/jem.20111187 – ident: e_1_2_11_30_1 doi: 10.1007/s00125-012-2753-4 – ident: e_1_2_11_66_1 doi: 10.2337/diabetes.55.04.06.db05-1261 – ident: e_1_2_11_58_1 doi: 10.1136/annrheumdis-2011-200690 – ident: e_1_2_11_82_1 doi: 10.1007/s00125-009-1390-z – ident: e_1_2_11_99_1 doi: 10.2337/db12-0098 – ident: e_1_2_11_102_1 doi: 10.1111/j.1600-6143.2010.03073.x – ident: e_1_2_11_12_1 doi: 10.1007/s00125-009-1642-y – year: 2012 ident: e_1_2_11_108_1 publication-title: Scientific Sessions of the American Diabetes Association – ident: e_1_2_11_8_1 doi: 10.2337/db10-1419 – ident: e_1_2_11_40_1 doi: 10.1056/NEJMoa1105143 – ident: e_1_2_11_41_1 doi: 10.1084/jem.176.6.1595 – ident: e_1_2_11_44_1 doi: 10.1056/NEJMoa0904452 – ident: e_1_2_11_59_1 doi: 10.1172/JCI28423 – ident: e_1_2_11_78_1 doi: 10.2337/db11-1033 – volume: 28 start-page: 924 year: 1996 ident: e_1_2_11_64_1 article-title: Islet protective effect of pravastatin from nonspecific inflammation in mouse pancreatic islet isografts publication-title: Transplant Proc – ident: e_1_2_11_81_1 doi: 10.2337/db08-0688 – ident: e_1_2_11_48_1 – ident: e_1_2_11_29_1 – volume: 163 start-page: 6275 year: 1999 ident: e_1_2_11_71_1 article-title: Determination of glutamic acid decarboxylase 65 peptides presented by the type I diabetes‐associated HLA‐DQ8 class II molecule identifies an immunogenic peptide motif publication-title: J Immunol doi: 10.4049/jimmunol.163.11.6275 – ident: e_1_2_11_36_1 doi: 10.1900/RDS.2004.1.80 – ident: e_1_2_11_65_1 doi: 10.1152/ajpendo.00132.2010 – ident: e_1_2_11_106_1 doi: 10.1097/TP.0b013e3181a9ee6c – ident: e_1_2_11_85_1 doi: 10.1172/JCI115946 – ident: e_1_2_11_51_1 doi: 10.1016/j.transproceed.2008.02.010 – ident: e_1_2_11_76_1 doi: 10.1172/JCI118919 – ident: e_1_2_11_83_1 – ident: e_1_2_11_46_1 doi: 10.1111/j.1399-5448.2011.00761.x – ident: e_1_2_11_13_1 doi: 10.1111/j.1365-2249.2008.03860.x – ident: e_1_2_11_23_1 doi: 10.1172/JCI0215488 – ident: e_1_2_11_10_1 doi: 10.1016/0167-5699(93)90163-F – ident: e_1_2_11_97_1 doi: 10.1146/annurev.iy.10.040192.001101 – ident: e_1_2_11_63_1 – ident: e_1_2_11_95_1 doi: 10.1182/blood-2011-09-377051 – ident: e_1_2_11_91_1 doi: 10.2337/dc09-0449 – ident: e_1_2_11_20_1 doi: 10.2337/db07-0416 – ident: e_1_2_11_33_1 doi: 10.1084/jem.166.4.982 – ident: e_1_2_11_26_1 doi: 10.1073/pnas.91.1.123 – ident: e_1_2_11_107_1 doi: 10.1097/TP.0b013e31817efc78 – ident: e_1_2_11_79_1 – ident: e_1_2_11_42_1 doi: 10.1016/j.clim.2011.12.005 – ident: e_1_2_11_62_1 – ident: e_1_2_11_74_1 doi: 10.1016/j.jaut.2009.10.005 – volume: 14 start-page: 1585 year: 2001 ident: e_1_2_11_19_1 article-title: Factors influencing remission phase in children with type 1 diabetes mellitus publication-title: J Pediatr Endocrinol Metab doi: 10.1515/JPEM.2001.14.9.1585 – ident: e_1_2_11_101_1 doi: 10.1046/j.1600-6143.2003.00351.x – volume: 160 start-page: 1717 year: 1998 ident: e_1_2_11_92_1 article-title: Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination publication-title: J Immunol doi: 10.4049/jimmunol.160.4.1717 – ident: e_1_2_11_90_1 doi: 10.1038/80525 – ident: e_1_2_11_34_1 doi: 10.1126/science.388619 – ident: e_1_2_11_93_1 doi: 10.1097/MED.0b013e32833aba41 – ident: e_1_2_11_9_1 – ident: e_1_2_11_11_1 doi: 10.1210/jc.81.12.4264 – ident: e_1_2_11_87_1 doi: 10.1016/j.humimm.2007.05.010 – ident: e_1_2_11_50_1 doi: 10.1073/pnas.0808031105 – ident: e_1_2_11_35_1 doi: 10.1073/pnas.89.8.3434 – ident: e_1_2_11_77_1 doi: 10.2337/dc11-0523 – ident: e_1_2_11_25_1 doi: 10.1172/JCI27191 – ident: e_1_2_11_68_1 doi: 10.2337/db12-0049 – ident: e_1_2_11_49_1 doi: 10.1111/j.1445-5994.1980.tb04101.x – volume: 46 start-page: 758 year: 1997 ident: e_1_2_11_60_1 article-title: Hsp60 peptide therapy of NOD mouse diabetes induces a Th2 cytokine burst and downregulates autoimmunity to various beta‐cell antigens publication-title: Diabetes doi: 10.2337/diab.46.5.758 – ident: e_1_2_11_3_1 doi: 10.1038/ni.1817 – ident: e_1_2_11_70_1 doi: 10.1038/nm1296-1348 – ident: e_1_2_11_52_1 doi: 10.1371/journal.pone.0033108 – ident: e_1_2_11_24_1 doi: 10.1016/j.bbrc.2007.11.077 – ident: e_1_2_11_96_1 doi: 10.1038/nm.2764 – ident: e_1_2_11_7_1 doi: 10.2337/db09-1378 – ident: e_1_2_11_104_1 doi: 10.1038/nm1673 – volume: 141 start-page: 1043 year: 1992 ident: e_1_2_11_31_1 article-title: Anti‐CD2 monoclonal antibodies prevent spontaneous and adoptive transfer of diabetes in the BB/Wor rat publication-title: Am J Pathol – ident: e_1_2_11_100_1 doi: 10.1056/NEJM200007273430401 – ident: e_1_2_11_47_1 doi: 10.1016/j.semarthrit.2012.03.004 – ident: e_1_2_11_84_1 doi: 10.2337/dc12-0038 – ident: e_1_2_11_67_1 doi: 10.2337/diabetes.51.3.638 – ident: e_1_2_11_28_1 doi: 10.1016/S0140-6736(11)60980-X – ident: e_1_2_11_5_1 doi: 10.2337/diabetes.54.5.1407 – ident: e_1_2_11_37_1 – ident: e_1_2_11_61_1 doi: 10.2337/db10-0560 – ident: e_1_2_11_16_1 doi: 10.1016/S1074-7613(00)80121-1 – ident: e_1_2_11_73_1 doi: 10.1056/NEJMoa0804328 – ident: e_1_2_11_21_1 doi: 10.1084/jem.20051224 – ident: e_1_2_11_86_1 doi: 10.2337/diabetes.52.8.1976 – ident: e_1_2_11_105_1 doi: 10.1097/TP.0b013e3181ff8772 – volume: 9 start-page: 1491 year: 2010 ident: e_1_2_11_32_1 article-title: Treatment of moderate‐to‐severe psoriasis with alefacept for up to one year: a case series publication-title: J Drugs Dermatol – ident: e_1_2_11_43_1 doi: 10.1016/S0140-6736(11)60886-6 – ident: e_1_2_11_27_1 doi: 10.1056/NEJMoa012864 – ident: e_1_2_11_53_1 – ident: e_1_2_11_72_1 – ident: e_1_2_11_94_1 doi: 10.1111/j.1600-6143.2004.00589.x
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Snippet	In type 1 diabetes (T1D) the immune system attacks insulin‐producing pancreatic β‐cells. Unfortunately, our ability to curb this pathogenic autoimmune response... In type 1 diabetes (T1D) the immune system attacks insulin-producing pancreatic β-cells. Unfortunately, our ability to curb this pathogenic autoimmune response... In type 1 diabetes (T1D) the immune system attacks insulin-producing pancreatic [beta]-cells. Unfortunately, our ability to curb this pathogenic autoimmune... In type 1 diabetes (T1D) the immune system attacks insulin-producing pancreatic beta -cells. Unfortunately, our ability to curb this pathogenic autoimmune...
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SubjectTerms	Animals Autoimmune diseases Autoimmunity beta cell Biomedical Research - trends clinical trial Diabetes diabetes mellitus Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - prevention & control Diabetes Mellitus, Type 1 - therapy Humans Immunotherapy - trends islets Islets of Langerhans Transplantation - immunology Islets of Langerhans Transplantation - trends Pancreas Pancreas - immunology Pancreas Transplantation - trends transplantation type 1 diabetes
Title	Emerging immune therapies in type 1 diabetes and pancreatic islet transplantation
URI	https://api.istex.fr/ark:/67375/WNG-93ZDWDD8-7/fulltext.pdf https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fdom.12046 https://www.ncbi.nlm.nih.gov/pubmed/23194064 https://www.proquest.com/docview/1364976799 https://www.proquest.com/docview/1365985288 https://www.proquest.com/docview/1399916890
Volume	15
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