B. O. Roep, J. Buckner, S. Sawcer, R. Toes, and F. Zipp, The problems and promises of research into human immunology and autoimmune disease, Nature Medicine, vol.476, issue.1, pp.18-48, 2012.
DOI : 10.1056/NEJMra020100

T. P. Di-lorenzo, M. Peakman, and B. O. Roep, Translational Mini-Review Series on Type 1 Diabetes:???Systematic analysis of T cell epitopes in autoimmune diabetes, Clinical & Experimental Immunology, vol.406, issue.Suppl. 2, pp.148-149, 2007.
DOI : 10.1111/j.1365-2249.2006.03244.x

J. M. Wenzlau, K. Juhl, L. Yu, O. Moua, S. A. Sarkar et al., The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes, Proceedings of the National Academy of Sciences, vol.104, issue.43, pp.17040-17045, 2007.
DOI : 10.1073/pnas.0705894104

J. F. Levy, O. Gautier, G. Launay, C. Bruno, L. A. Boitard et al., Zinc transporter (ZnT)8(186-194) is an immunodominant CD8 (+) T cell epitope in HLA-A2 (+) type 1 diabetic patients, Diabetologia, pp.55-2026, 2012.

B. O. Roep, T-cell responses to autoantigens in IDDM. The search for the Holy Grail, Diabetes, pp.45-1147, 1996.

P. J. Bingley, E. Bonifacio, A. G. Ziegler, D. A. Schatz, M. A. Atkinson et al., Proposed guidelines on screening for risk of type 1 diabetes, Diabetes Care, pp.24-398, 2001.

S. Culina and R. Mallone, Immune biomarkers in immunotherapeutic trials for type 1 diabetes: Cui prodest?, Diabetes & Metabolism, vol.38, issue.5, pp.379-385, 2012.
DOI : 10.1016/j.diabet.2012.05.005

. Herrath, Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients, J. Exp. Med, vol.209, pp.51-60, 2012.

G. S. Eisenbarth and B. Lecture, An unfinished journey: molecular pathogenesis to prevention of type 1A diabetes, Diabetes, pp.59-759, 2009.

M. C. Malmegrim, B. P. Foss-freitas, M. C. Simoes, E. Foss, R. K. Squiers et al., Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus, JAMA, pp.297-1568, 2007.

R. Mallone and V. Brezar, To B or Not to B: (Anti)bodies of Evidence on the Crime Scene of Type 1 Diabetes?, Diabetes, vol.60, issue.8
DOI : 10.2337/db11-0700

A. G. Herold and . Daifotis, Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial, Lancet, pp.378-487, 2011.

J. F. Bach, Anti-CD3 antibodies for type 1 diabetes: beyond expectations, The Lancet, vol.378, issue.9790, pp.378-459, 2011.
DOI : 10.1016/S0140-6736(11)60980-X

J. G. Zucman, J. C. Guillet, S. Carel, J. Muller, C. Choppin et al., Recognition of a subregion of human proinsulin by class I-restricted T cells in type 1 diabetic patients, Proc. Natl. Acad. Sci. U.S.A, vol.102, pp.10581-10586, 2005.

J. M. Chatenoud, P. Bach, and . Van-endert, CD8+ T-cell responses identify beta-cell autoimmunity in human type 1 diabetes, Diabetes, pp.56-613, 2007.

C. Autoreactive, Cells Specific for Different Islet Cell-Associated Epitopes Using Combinatorial MHC Multimers, Diabetes, pp.59-1721, 2010.

O. Leymarie, F. A. Launay, S. Lemonnier, J. C. Buus, C. Carel et al., HLA-B7-Restricted Islet Epitopes Are Differentially Recognized in Type 1 Diabetic Children and Adults and Form Weak Peptide-HLA Complexes, Diabetes, pp.61-2546, 2012.

J. W. Pipeleers, B. O. Drijfhout, and . Roep, Autoreactive CD8 T cells associated with beta cell destruction in type 1 diabetes, Proc. Natl. Acad. Sci. U.S.A, vol.102, pp.18425-18430, 2005.

E. Enee, E. Martinuzzi, P. Blancou, J. M. Bach, R. Mallone et al., Equivalent Specificity of Peripheral Blood and Islet-Infiltrating CD8+ T Lymphocytes in Spontaneously Diabetic HLA-A2 Transgenic NOD Mice, The Journal of Immunology, vol.180, issue.8, pp.180-5430, 2008.
DOI : 10.4049/jimmunol.180.8.5430

G. C. Marchetti, E. N. Huang, R. Gurzov, D. L. Pujol-borrell, M. Eizirik et al., Peripheral and islet interleukin-17 pathway activation characterizes human autoimmune diabetes and promotes cytokine-mediated beta-cell death, Diabetes, pp.60-2112, 2011.

. Boitard, Single Insulin-Specific CD8+ T Cells Show Characteristic Gene Expression Profiles in Human Type 1
URL : https://hal.archives-ouvertes.fr/hal-00645775

M. Peakman, CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope, J. Clin. Invest, vol.118, pp.3390-3402, 2008.

A. G. Van-halteren, M. J. Kardol, A. Mulder, and B. O. Roep, Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice, Diabetologia, vol.48, issue.1, pp.48-75, 2005.
DOI : 10.1007/s00125-004-1613-2

I. Jarchum, J. C. Baker, T. Yamada, T. Takaki, M. P. Marron et al., In Vivo Cytotoxicity of Insulin-Specific CD8+ T-Cells in HLA-A*0201 Transgenic NOD Mice, Diabetes, vol.56, issue.10, pp.56-2551, 2007.
DOI : 10.2337/db07-0332

L. D. Serreze, M. Shultz, J. W. Griffioen, D. L. Drijfhout, B. O. Greiner et al., Islet-Specific CTL Cloned from a Type 1 Diabetes Patient Cause Beta-Cell Destruction after Engraftment into HLA-A2 Transgenic NOD, PLoS One, vol.7, p.49213, 2012.

E. Martinuzzi, G. Novelli, M. Scotto, P. Blancou, J. M. Bach et al., The Frequency and Immunodominance of Islet-Specific CD8+ T-cell Responses Change after Type 1 Diabetes Diagnosis and Treatment, Diabetes, vol.57, issue.5, pp.57-1312, 2008.
DOI : 10.2337/db07-1594

URL : https://hal.archives-ouvertes.fr/inserm-00266516

M. Akerblom and . Knip, Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. The Childhood Diabetes in Finland Study Group, J. Clin. Invest, vol.101, pp.327-336, 1998.

D. J. Klinke, Extent of Beta Cell Destruction Is Important but Insufficient to Predict the Onset of Type 1 Diabetes Mellitus, PLoS ONE, vol.51, issue.1
DOI : 10.1371/journal.pone.0001374.s001

C. J. Greenbaum, T. Mandrup-poulsen, P. F. Mcgee, T. Battelino, B. Haastert et al., Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes, Diabetes Care, pp.31-1966, 2008.

B. O. Roep and M. Peakman, Surrogate end points in the design of immunotherapy trials: emerging lessons from type 1 diabetes, Nature Reviews Immunology, vol.27, issue.2, pp.145-152, 2010.
DOI : 10.1038/nri2705

P. Weets, P. Rebello, E. Bird, M. Berrie, H. Frewin et al., Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes, N. Engl. J. Med, pp.352-2598, 2005.

J. M. Wilson, J. S. Lachin, and . Skyler, Rituximab, B-lymphocyte depletion, and preservation of beta-cell function

L. Yu, K. Herold, H. Krause-steinrauf, P. L. Mcgee, B. Bundy et al., Rituximab Selectively Suppresses Specific Islet Antibodies, Diabetes, vol.60, issue.10, pp.60-2560, 2011.
DOI : 10.2337/db11-0674

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178300

C. Ivarsson, A. Johansson, N. O. Lindh, J. Nilsson, E. Aman et al., GAD treatment and insulin secretion in recent-onset type 1 diabetes, N. Engl. J. Med, p.359, 1909.

L. -. Casas, Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes, PLoS One, vol.6, p.29008, 2011.

H. Reijonen, T. L. Daniels, A. Lernmark, and G. T. Nepom, GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65, Diabetes, vol.49, issue.10, pp.49-1621, 2000.
DOI : 10.2337/diabetes.49.10.1621

. Colman, Pancreatic beta-cell function and immune responses to insulin after administration of intranasal insulin to humans at risk for type 1 diabetes, Diabetes Care, vol.27, pp.2348-2355, 2004.

V. Brezar, J. C. Carel, C. Boitard, and R. Mallone, Beyond the Hormone: Insulin as an Autoimmune Target in Type 1 Diabetes, Endocrine Reviews, vol.32, issue.5, pp.32-623, 2011.
DOI : 10.1210/er.2011-0010

V. Brezar, S. Culina, M. C. Gagnerault, and R. Mallone, Short-term subcutaneous insulin treatment delays but does not prevent diabetes in NOD mice, European Journal of Immunology, vol.339, issue.Suppl 1, pp.42-1553, 2012.
DOI : 10.1002/eji.201242394

M. Pawelec, B. O. Roederer, P. Roep, S. H. Romero, S. Van-der-burg et al., Davis, T cell assays and MIATA: the essential minimum for maximum impact, Immunity, pp.37-38, 2012.

. Schloot, Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society, Clin. Exp. Immunol, pp.163-196, 2011.

M. Peakman, T. I. Tree, J. Endl, E. P. Van, M. A. Atkinson et al., Characterization of preparations of GAD65, proinsulin, and the islet tyrosine phosphatase IA-2 for use in detection of autoreactive

B. O. Roep, M. A. Atkinson, P. M. Van-endert, P. A. Gottlieb, S. B. Wilson et al., Autoreactive T cell Responses in Insulin-dependent (Type 1) Diabetes Mellitus. Report of the First International Workshop for Standardization of T cell assays, Journal of Autoimmunity, vol.13, issue.2, pp.13-267, 1999.
DOI : 10.1006/jaut.1999.0312

. Mallone, Current approaches to measuring human islet-antigen specific T cell function in type 1 diabetes

H. F. Frank, R. Mcfarland, and . Martin, 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, vol.6, pp.1167-1175, 2000.

M. M. Davis, A Prescription for Human Immunology, Immunity, vol.29, issue.6, pp.29-835, 2008.
DOI : 10.1016/j.immuni.2008.12.003

S. Culina, C. Boitard, and R. Mallone, Antigen-Based Immune Therapeutics for Type 1 Diabetes: Magic Bullets or Ordinary Blanks?, Clinical and Developmental Immunology, vol.65, issue.8, p.2011, 2011.
DOI : 10.1007/s11892-008-0017-y

S. Fourlanos, C. Perry, S. A. Gellert, E. Martinuzzi, R. Mallone et al., Evidence That Nasal Insulin Induces Immune Tolerance to Insulin in Adults With Autoimmune Diabetes, Diabetes, vol.60, issue.4, pp.60-1237, 2011.
DOI : 10.2337/db10-1360

V. A. Huurman, P. E. Van-der-meide, G. Duinkerken, S. Willemen, I. R. Cohen et al., Immunological efficacy of heat shock protein 60 peptide DiaPep277 therapy in clinical type I diabetes

D. M. Harlan, N. S. Kenyon, O. Korsgren, and B. O. Roep, Current Advances and Travails in Islet Transplantation, Diabetes, vol.58, issue.10, pp.58-2175, 2009.
DOI : 10.2337/db09-0476

B. O. Roep, I. Stobbe, G. Duinkerken, J. J. Van-rood, A. Lernmark et al., Auto- and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients, Diabetes, vol.48, issue.3, pp.48-484, 1999.
DOI : 10.2337/diabetes.48.3.484

F. H. Roelen, B. Claas, D. G. Keymeulen, B. O. Pipeleers, and . Roep, Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation, PLoS One, vol.3, p.2435, 2008.

B. O. Gorus, D. G. Roep, B. Pipeleers, and . Keymeulen, Differences in baseline lymphocyte counts and autoreactivity are associated with differences in outcome of islet cell transplantation in type 1 diabetic patients, Diabetes, pp.58-2267, 2009.

V. A. Huurman, J. H. Velthuis, R. Hilbrands, T. I. Tree, P. Gillard et al., Allograft-Specific Cytokine Profiles Associate with Clinical Outcome After Islet Cell Transplantation, American Journal of Transplantation, vol.178, issue.2, pp.382-388, 2009.
DOI : 10.1111/j.1600-6143.2008.02479.x

B. O. Glass and . Roep, Tolerance to kidney allograft transplanted into Type I diabetic patients persists after in vivo challenge with pancreatic islet allografts that express repeated mismatches, Diabetologia, pp.42-1379, 1999.

F. H. Pipeleers, B. O. Claas, and . Roep, Alloreactivity against repeated HLA mismatches of sequential islet grafts transplanted in non-uremic type 1 diabetes patients, Transplantation, pp.80-118, 2005.

A. Saif, J. R. Lakey, and A. M. Shapiro, Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation, Am. J. Transplant, vol.7, pp.1242-1248, 2007.

P. M. Campbell, P. A. Senior, A. Salam, K. Labranche, D. L. Bigam et al., High Risk of Sensitization After Failed Islet Transplantation, American Journal of Transplantation, vol.174, issue.10, pp.2311-2317, 2007.
DOI : 10.1016/j.trim.2005.01.001

B. Pipeleers and . Keymeulen, Graves hyperthyroidism after stopping immunosuppressive therapy in type 1 diabetic Islet cell recipients with pretransplant TPO autoantibodies, Diabetes Care, vol.32, pp.1817-1819, 2009.

E. Bosi, S. Braghi, P. Maffi, M. Scirpoli, F. Bertuzzi et al., Autoantibody Response to Islet Transplantation in Type 1 Diabetes, Diabetes, vol.50, issue.11, pp.50-2464, 2001.
DOI : 10.2337/diabetes.50.11.2464

C. Jaeger, M. D. Brendel, M. Eckhard, and R. G. Bretzel, Islet autoantibodies as potential markers for disease recurrence in clinical islet transplantation, Experimental and Clinical Endocrinology & Diabetes, vol.108, issue.5, pp.328-333, 2000.
DOI : 10.1055/s-2000-8125

. Keymeulen, Comparison of sirolimus alone with sirolimus plus tacrolimus in type 1 diabetic recipients of cultured islet cell grafts, Transplantation, pp.85-256, 2008.

C. Versteeg-van-der-voort-maarschalk, B. Mathieu, D. G. Keymeulen, B. O. Pipeleers, F. H. Roep et al., Relevance of cytotoxic alloreactivity under different immunosuppressive regimens in clinical islet cell transplantation, Clin. Exp. Immunol, pp.156-141, 2009.

. Bonifacio, Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells, J. Clin. Invest, vol.118, pp.1806-1814, 2008.

F. H. Gorus, B. Claas, D. L. Keymeulen, D. G. Roelen, B. O. Pipeleers et al., Immune responses against islet allografts during tapering of immunosuppression--a pilot study in 5 subjects, Clin. Exp. Immunol, pp.169-190, 2012.

H. P. Mervis, E. Chase, and . Leschek, Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1, Diabetes Care, pp.28-1068, 2005.

S. Culina and R. Mallone, Pathogenic and Regulatory T Cells in Type 1 Diabetes: Losing Self-Control, Restoring It, and How to Take the Temperature, Current Diabetes Reports, vol.60, issue.5, pp.11-426, 2011.
DOI : 10.1007/s11892-011-0209-8

T. I. Tree, J. Lawson, H. Edwards, A. Skowera, S. Arif et al., Naturally arising human CD4 T cells that recognize islet autoantigens and secrete IL-10 regulate pro-inflammatory T cell responses via linked suppression, Diabetes, pp.59-1451, 2010.

. Weissleder, Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients, J. Clin. Invest, vol.121, pp.442-445, 2011.

Z. Medarova and A. Moore, MRI as a tool to monitor islet transplantation, Nature Reviews Endocrinology, vol.3, issue.8, pp.444-452, 2009.
DOI : 10.1038/nrendo.2009.130