Immunology of β-cell destruction

Advances in Experimental Medicine and Biology

Volumn 654, Issue , 2010, Pages 537-583

  La Torre, Daria ^a   Lernmark, Åke ^b  

^a LUND UNIVERSITY   (Sweden)

^b NONE

Author keywords

Antigen presenting cells; Autoantigens; CD4+ T cells; CD8+ T cells; Dendritic cells; Insulitis; Islet autoantibodies; Islet autoimmunity; Prediction; Prevention; T regulatory cells

Indexed keywords

ALLOXAN; AUTOANTIGEN; BASIC LEUCINE ZIPPER TRANSCRIPTION FACTOR; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; EPIDERMAL GROWTH FACTOR RECEPTOR 3; GAMMA INTERFERON; GLUTAMATE DECARBOXYLASE 65; HLA DQ ANTIGEN; HLA DQ2 ANTIGEN; HLA DQ6.2 ANTIGEN; HLA DQ8 ANTIGEN; HLA DQA1 ANTIGEN; INOSITOL 1,4,5 TRISPHOSPHATE RECEPTOR; INOSITOL 1,4,5 TRISPHOSPHATE RECEPTOR 3; INSULIN; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 35; INTERLEUKIN 4; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 2; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 22; STREPTOZOCIN; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA1; TYROSINE 3 MONOOXYGENASE; UNCLASSIFIED DRUG; VACOR; VIRUS ANTIGEN; ZINC TRANSPORTER;

ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; ARTICLE; AUTOIMMUNITY; B LYMPHOCYTE; CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DESTRUCTION; CELL KILLING; CELLULAR DISTRIBUTION; CHROMOSOME 6; CYTOKINE PRODUCTION; CYTOTOXIC T LYMPHOCYTE; CYTOTOXICITY; DENDRITIC CELL; ENVIRONMENTAL FACTOR; GENETIC POLYMORPHISM; GENETIC SUSCEPTIBILITY; HELPER CELL; HISTORY OF MEDICINE; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; INSULIN DEPENDENT DIABETES MELLITUS; INSULITIS; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE HOMING; MAJOR HISTOCOMPATIBILITY COMPLEX; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REGULATORY T LYMPHOCYTE; TOXIN ANALYSIS; VIRUS INFECTION; ANIMAL; BIOLOGICAL MODEL; CHEMISTRY; CYTOLOGY; ENVIRONMENT; LYMPH NODE; MOUSE; PANCREAS ISLET; PATHOLOGY; RAT; REVIEW;

MUS; RATTUS; RODENTIA;

ANIMALS; ANTIGEN PRESENTATION; AUTOANTIGENS; AUTOIMMUNITY; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; ENVIRONMENT; HUMANS; INSULIN-SECRETING CELLS; ISLETS OF LANGERHANS; LYMPH NODES; MICE; MODELS, BIOLOGICAL; RATS;

EID: 77953924891     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-90-481-3271-3_24     Document Type: Article

References (390)

1. McDevitt H, Singer S, Tisch R. The role of MHC class II genes in susceptibility and resistance to type I diabetes mellitus in the NOD mouse. Horm Metab Res 1996;28:287-8. (Pubitemid 126425523)
2. Eisenbarth GS, Jeffrey J. The natural history of type 1A diabetes. Arq Bras Endocrinol Metabol 2008;52:146-55.
3. Bach JF. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev 1994;15:516-42.
4. Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001;358:221-9. (Pubitemid 32718550)
5. Staeva-Vieira T, Peakman M, von Herrath M. Translational mini-review series on type 1 diabetes: Immune-based therapeutic approaches for type 1 diabetes. Clin Exp Immunol 2007;148:17-31. (Pubitemid 46364996)
6. Haller MJ, Atkinson MA, Schatz D. Type 1 diabetes mellitus: etiology, presentation, and management. Pediatr Clin North Am 2005;52:1553-78. (Pubitemid 41654729)
7. Weichselbaum A. Über die veränderungen des pankreas bei diabetes mellitus. Sitzungsber Akad Wiss Wien Math Naturw Klasse 1910;119:73-281.
8. Von Meyenburg H. Über "insulitis" bei diabetes. Schweitz Med Wochenschr 1940;21: 554-61.
9. Gepts W, De Mey J. Islet cell survival determined by morphology. An immunocytochemical study of the islets of Langerhans in juvenile diabetes mellitus. Diabetes 1978;27 Suppl 1:251-61. (Pubitemid 8303582)
10. Gepts W, Lecompte PM. The pancreatic islets in diabetes. Am J Med 1981;70:105-15.
11. Itoh N, Hanafusa T, Miyazaki A, Miyagawa J, Yamagata K, Yamamoto K, Waguri M, Imagawa A, Tamura S, Inada M. et al. Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients. J Clin Invest 92:2313-2322, 1993 (Pubitemid 23333537)
12. Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med 1985;313:353-60. (Pubitemid 15046367)
13. In't Veld PA, Pipeleers DG. In situ analysis of pancreatic islets in rats developing diabetes. Appearance of nonendocrine cells with surface MHC class II antigens and cytoplasmic insulin immunoreactivity. J Clin Invest 1988;82:1123-1128.
14. Variation and trends in incidence of childhood diabetes in Europe. EURODIAB ACE Study Group. Lancet 2000;355:873-876.
15. Soltesz G, Patterson CC, Dahlquist G. Worldwide childhood type 1 diabetes incidence - what can we learn from epidemiology? Pediatr Diabetes 2007;8 Suppl 6:6-14.
16. Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, Tuomilehto J. Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. Diabetes Care 2000;23:1516-26.
17. Standards of medical care in diabetes - 2008. Diabetes Care 2008;31 Suppl 1:S12-54.
18. Harjutsalo V, Sjoberg L, Tuomilehto J. Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet 2008;371:1777-82. (Pubitemid 351697953)
19. Todd JA, Farrall M. Panning for gold: genome-wide scanning for linkage in type 1 diabetes. Hum Mol Genet 1996;5 Spec No:1443-48.
20. Akesson K, Nystrom L, Farnkvist L, Ostman J, Lernmark A, Kockum I. Increased risk of diabetes among relatives of female insulin-treated patients diagnosed at 15-34 years of age. Diabet Med 2005;22:1551-1557 (Pubitemid 41641163)
21. Ungar B, Stocks AE, Martin FI, Whittingham S, Mackay IR. Intrinsic-factor antibody, parietal-cell antibody, and latent pernicious anaemia in diabetes mellitus. Lancet 2:415-7, 1968.
22. Nerup J, Binder C. Thyroid, gastric and adrenal auto-immunity in diabetes mellitus. Acta Endocrinol (Copenh) 1973;72:279-86.
23. Barker JM. Clinical review: Type 1 diabetes-associated autoimmunity: natural history, genetic associations, and screening. J Clin Endocrinol Metab 2006;91:1210-17.
24. Nerup J, Andersen OO, Bendixen G, Egeberg J, Poulsen JE, Vilien M, Westrup M. Antipancreatic, cellular hypersensitivity in diabetes mellitus. Experimental induction of antipancreatic, cellular hypersensitivity and associated morphological B-cell changes in the rat. Acta Allergol 1973;28:231-49.
25. Nerup J, Platz P, Andersen OO, Christy M, Lyngsoe J, Poulsen JE, Ryder LP, Nielsen LS, Thomsen M, Svejgaard A. HL-A antigens and diabetes mellitus. Lancet 1974;2:864-6.
26. Erlich H, Valdes AM, Noble J, Carlson JA, Varney M, Concannon P, Mychaleckyj JC, Todd JA, Bonella P, Fear AL, Lavant E, Louey A, Moonsamy P. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes 2008;57:1084-92.
27. Ilonen J, Sjoroos M, Knip M, Veijola R, Simell O, Akerblom HK, Paschou P, Bozas E, Havarani B, Malamitsi-Puchner A, Thymelli J, Vazeou A, Bartsocas CS. Estimation of genetic risk for type 1 diabetes. Am J Med Genet 2002;115:30-36. (Pubitemid 34650720)
28. Sanjeevi CB. HLA-DQ6-mediated protection in IDDM. Hum Immunol 2000;61:148-53. (Pubitemid 30075236)
29. Thorsby E, Lie BA. HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms. Transpl Immunol 2005;14:175-82. (Pubitemid 40848523)
30. Wucherpfennig KW. Insights into autoimmunity gained from structural analysis of MHCpeptide complexes. Curr Opin Immunol 2001;13:650-6. (Pubitemid 33000157)
31. Moustakas AK, Papadopoulos GK. Molecular properties of HLA-DQ alleles conferring susceptibility to or protection from insulin-dependent diabetes mellitus: keys to the fate of islet beta-cells. Am J Med Genet 2002;115:37-47. (Pubitemid 34650721)
32. Cucca F, Lampis R, Congia M, Angius E, Nutland S, Bain SC, Barnett AH, Todd JA. A correlation between the relative predisposition of MHC class II alleles to type 1 diabetes and the structure of their proteins. Hum Mol Genet 2001;10:2025-37. (Pubitemid 32998815)
33. van der Werf N, Kroese FG, Rozing J, Hillebrands JL. Viral infections as potential triggers of type 1 diabetes. Diabetes Metab Res Rev 2007;23:169-83. (Pubitemid 46437842)
34. Jun HS, Yoon JW. A new look at viruses in type 1 diabetes. Diabetes Metab Res Rev 2003;19:8-31.
35. Dahlquist GG. Viruses and other perinatal exposures as initiating events for beta-cell destruction. Ann Med 1997;29:413-7. (Pubitemid 27520569)
36. Dahlquist G, Blom L, Lonnberg G. The Swedish Childhood Diabetes Study - a multivariate analysis of risk determinants for diabetes in different age groups. Diabetologia 1991;34: 757-62.
37. Gerstein HC. Cow's milk exposure and type I diabetes mellitus. A critical overview of the clinical literature. Diabetes Care 1994;17:13-9.
38. Vaarala O. Environmental causes: dietary causes. Endocrinol Metab Clin North Am 2004;33:17-26, vii.
39. Martin JM, Trink B, Daneman D, Dosch HM, Robinson B. Milk proteins in the etiology of insulin-dependent diabetes mellitus (IDDM). Ann Med 1991;23:447-52.
40. Schranz DB, Lernmark A. Immunology in diabetes: an update. Diabetes Metab Rev 1998;14:3-29. (Pubitemid 28207034)
41. Dahlquist GG, Blom LG, Persson LA, Sandstrom AI, Wall SG. Dietary factors and the risk of developing insulin dependent diabetes in childhood. BMJ 1990;300:1302-6. (Pubitemid 20164760)
42. Blom L, Nystrom L, Dahlquist G. The Swedish childhood diabetes study. Vaccinations and infections as risk determinants for diabetes in childhood. Diabetologia 1991;34:176-81.
43. Helmke K, Otten A, Willems WR, Brockhaus R, Mueller-Eckhardt G, Stief T, Bertrams J, Wolf H, Federlin K. Islet cell antibodies and the development of diabetes mellitus in relation to mumps infection and mumps vaccination. Diabetologia 1986;29:30-3. (Pubitemid 16162738)
44. Akerblom HK, Vaarala O, Hyoty H, Ilonen J, Knip M. Environmental factors in the etiology of type 1 diabetes. Am J Med Genet 2002;115:18-29. (Pubitemid 34657185)
45. Lo SS, Tun RY, Hawa M, Leslie RD. Studies of diabetic twins. Diabetes Metab Rev 1991;7:223-38.
46. Barnett AH, Eff C, Leslie RD, Pyke DA. Diabetes in identical twins. A study of 200 pairs. Diabetologia 1981;20:87-93. (Pubitemid 11138466)
47. Kyvik KO, Green A, Beck-Nielsen H. Concordance rates of insulin dependent diabetes mellitus: a population based study of young Danish twins. BMJ 1995;311:913-7.
48. Tuomilehto J. Epidemiology of childhood diabetes in the Baltic area. Nord Med 1992;107:244-6. 260
49. Geographic patterns of childhood insulin-dependent diabetes mellitus. Diabetes Epidemiology Research International Group. Diabetes 1988;37:1113-9.
50. Anderson MS, Bluestone JA. The NOD mouse: a model of immune dysregulation. Annu Rev Immunol 2005;23:447-85. (Pubitemid 40563177)
51. Yang Y, Santamaria P. Lessons on autoimmune diabetes from animal models. Clin Sci 2006; (Lond) 110:627-39. (Pubitemid 43844732)
52. Uibo R, Lernmark A. GAD65 autoimmunity-clinical studies. Adv Immunol 2008;100: 39-78.
53. Bottazzo GF, Florin-Christensen A, Doniach D. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 1974;2:1279-83.
54. Lernmark A, Freedman ZR, Hofmann C, Rubenstein AH, Steiner DF, Jackson RL, Winter RJ, Traisman HS. Islet-cell-surface antibodies in juvenile diabetes mellitus. N Engl J Med 1978;299:375-80. (Pubitemid 9009389)
55. Baekkeskov S, Nielsen JH, Marner B, Bilde T, Ludvigsson J, Lernmark A. Autoantibodies in newly diagnosed diabetic children immunoprecipitate human pancreatic islet cell proteins. Nature 1982;298:167-9. (Pubitemid 12087509)
56. Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, De Camilli P. Identification of the 64 K autoantigen in insulindependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 1990;347:151-6.
57. Karlsen AE, Hagopian WA, Grubin CE, Dube S, Disteche CM, Adler DA, Barmeier H, Mathewes S, Grant FJ, Foster D, et al.: Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. Proc Natl Acad Sci U S A 1991;88:8337-41. (Pubitemid 21915351)
58. Marshall MO, Hoyer PE, Petersen JS, Hejnaes KR, Genovese S, Dyrberg T, Bottazzo GF. Contribution of glutamate decarboxylase antibodies to the reactivity of islet cell cytoplasmic antibodies. J Autoimmun 1994;7:497-508. (Pubitemid 24268388)
59. Palmer JP, Asplin CM, Clemons P, Lyen K, Tatpati O, Raghu PK, Paquette TL. Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 1983;222: 1337-9. (Pubitemid 14204704)
60. Christie MR, Vohra G, Champagne P, Daneman D, Delovitch TL. Distinct antibody specificities to a 64-kD islet cell antigen in type 1 diabetes as revealed by trypsin treatment. J Exp Med 1990;172:789-94. (Pubitemid 20301225)
61. Lan MS, Lu J, Goto Y, Notkins AL. Molecular cloning and identification of a receptortype protein tyrosine phosphatase, IA-2, from human insulinoma. DNA Cell Biol 1994;13: 505-14. (Pubitemid 24291404)
62. Kawasaki E, Yu L, Rewers MJ, Hutton JC, Eisenbarth GS. Definition of multiple ICA512/phogrin autoantibody epitopes and detection of intramolecular epitope spreading in relatives of patients with type 1 diabetes. Diabetes 1998;47:733-42. (Pubitemid 28201802)
63. Saeki K, Zhu M, Kubosaki A, Xie J, LanMS, Notkins AL. Targeted disruption of the protein tyrosine phosphatase-like molecule IA-2 results in alterations in glucose tolerance tests and insulin secretion. Diabetes 2002;51:1842-50. (Pubitemid 34564297)
64. Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, Rewers M, Eisenbarth GS, Jensen J, Davidson HW, Hutton JC. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 2007;104:17040-5. (Pubitemid 350210987)
65. Wenzlau JM, Hutton JC, Davidson HW. New antigenic targets in type 1 diabetes. Curr Opin Endocrinol Diabetes Obes 2008;15:315-20.
66. Chang YH, Hwang J, Shang HF, Tsai ST. Characterization of human DNA topoisomerase II as an autoantigen recognized by patients with IDDM. Diabetes 1996;45:408-14. (Pubitemid 26110244)
67. Ozawa Y, Kasuga A, Nomaguchi H, Maruyama T, Kasatani T, Shimada A, Takei I, Miyazaki J, Saruta T. Detection of autoantibodies to the pancreatic islet heat shock protein 60 in insulin-dependent diabetes mellitus. J Autoimmun 1996;9:517-24. (Pubitemid 26273642)
68. Abulafia-Lapid R, Gillis D, Yosef O, Atlan H, Cohen IR. T cells and autoantibodies to human HSP70 in type 1 diabetes in children. J Autoimmun 2003;20:313-21. (Pubitemid 36677523)
69. Qin HY, Mahon JL, Atkinson MA, Chaturvedi P, Lee-Chan E, Singh B. Type 1 diabetes alters anti-hsp90 autoantibody isotype. J Autoimmun 2003;20:237-45. (Pubitemid 36561489)
70. Hirai H, Miura J, Hu Y, Larsson H, Larsson K, Lernmark A, Ivarsson SA, Wu T, Kingman A, Tzioufas AG, Notkins AL. Selective screening of secretory vesicle-associated proteins for autoantigens in type 1 diabetes: VAMP2 and NPY are new minor autoantigens. Clin Immunol 2008;127:366-74.
71. Castano L, Russo E, Zhou L, Lipes MA, Eisenbarth GS. Identification and cloning of a granule autoantigen (carboxypeptidase-H) associated with type I diabetes. J Clin Endocrinol Metab 1991;73:1197-201. (Pubitemid 121000692)
72. Martin S, Kardorf J, Schulte B, Lampeter EF, Gries FA, Melchers I, Wagner R, Bertrams J, Roep BO, Pfutzner A. Autoantibodies to the islet antigen ICA69 occur in IDDM and in rheumatoid arthritis. Diabetologia 1995;38:351-5.
73. Pupilli C, Giannini S, Marchetti P, Lupi R, Antonelli A, Malavasi F, Takasawa S, Okamoto H, Ferrannini E. Autoantibodies to CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in Caucasian patients with diabetes: effects on insulin release from human islets. Diabetes 1999;48:2309-15. (Pubitemid 30395421)
74. Kasimiotis H, Fida S, Rowley MJ, Mackay IR, Zimmet PZ, Gleason S, Rabin DU, Myers MA. Antibodies to SOX13 (ICA12) are associated with type 1 diabetes. Autoimmunity 2001;33:95-101. (Pubitemid 32293977)
75. Ikehata F, Satoh J, Nata K, Tohgo A, Nakazawa T, Kato I, Kobayashi S, Akiyama T, Takasawa S, Toyota T, Okamoto H. Autoantibodies against CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin- dependent diabetes patients. J Clin Invest 1998;102:395-401. (Pubitemid 28335199)
76. Torn C, Shtauvere-Brameus A, Sanjeevi CB, Landin-Olsson M. Increased autoantibodies to SOX13 in Swedish patients with type 1 diabetes. Ann N Y Acad Sci 2002;958:218-23. (Pubitemid 34592231)
77. Gillard BK, Thomas JW, Nell LJ, Marcus DM. Antibodies against ganglioside GT3 in the sera of patients with type I diabetes mellitus. J Immunol 1989;142:3826-32. (Pubitemid 19164410)
78. Dotta F, Gianani R, Previti M, Lenti L, Dionisi S, D'Erme M, Eisenbarth GS, Di Mario U. Autoimmunity to the GM2-1 islet ganglioside before and at the onset of type I diabetes. Diabetes 1996;45:1193-6. (Pubitemid 26296318)
79. Buschard K, Josefsen K, Horn T, Fredman P. Sulphatide and sulphatide antibodies in insulindependent diabetes mellitus. Lancet 1993;342:840. (Pubitemid 23285913)
80. Aanstoot HJ, Kang SM, Kim J, Lindsay LA, Roll U, Knip M, Atkinson M, Mose-Larsen P, Fey S, Ludvigsson J, Landin L, Bruining J, Maclaren N, Akerblom HK, Baekkeskov S. Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. J Clin Invest 1996;97:2772-83.
81. Petersen JS, Hejnaes KR, Moody A, Karlsen AE, Marshall MO, Hoier-Madsen M, Boel E, Michelsen BK, Dyrberg T. Detection of GAD65 antibodies in diabetes and other autoimmune diseases using a simple radioligand assay. Diabetes 1994;43:459-67.
82. Schmidli RS, Colman PG, Bonifacio E. Disease sensitivity and specificity of 52 assays for glutamic acid decarboxylase antibodies. The Second International GADAB Workshop. Diabetes 1995;44:636-40.
83. Torn C, Mueller PW, Schlosser M, Bonifacio E, Bingley PJ. Diabetes Antibody Standardization Program: evaluation of assays for autoantibodies to glutamic acid decarboxylase and islet antigen-2. Diabetologia 2008;51:846-52.
84. Mire-Sluis AR, Gaines Das R, Lernmark A. The World Health Organization International Collaborative Study for islet cell antibodies. Diabetologia 2000;43:1282-92.
85. Pihoker C, Gilliam LK, Hampe CS, Lernmark A. Autoantibodies in diabetes. Diabetes Suppl 54 2005;2:S52-61. (Pubitemid 43343331)
86. Lynch KF, Lernmark B, Merlo J, Cilio CM, Ivarsson SA, Lernmark A. Cord blood islet autoantibodies and seasonal association with the type 1 diabetes high-risk genotype. J Perinatol 2008;28:211-7. (Pubitemid 351338613)
87. Yoon JW, Jun HS. Autoimmune destruction of pancreatic beta-cells. Am J Ther 2005;12:580-91.
88. Silveira PA, Grey ST. B cells in the spotlight: innocent bystanders or major players in the pathogenesis of type 1 diabetes. Trends Endocrinol Metab 2006;17:128-35.
89. Delovitch TL, Singh B. The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity 1997;7:727-38. (Pubitemid 28064887)
90. DiLorenzo TP, Serreze DV. The good turned ugly: immunopathogenic basis for diabetogenic CD8+ T cells in NOD mice. Immunol Rev 2005;204:250-63. (Pubitemid 40460506)
91. Toma A, Haddouk S, Briand JP, Camoin L, Gahery H, Connan F, Dubois-Laforgue D, Caillat-Zucman S, Guillet JG, Carel JC, Muller S, Choppin J, Boitard C. 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 2005;102:10581-6. (Pubitemid 41061597)
92. Panina-Bordignon P, Lang R, van Endert PM, Benazzi E, Felix AM, Pastore RM, Spinas GA, Sinigaglia F. Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. J Exp Med 1995;181:1923-7.
93. Dromey JA, Weenink SM, Peters GH, Endl J, Tighe PJ, Todd I, Christie MR. Mapping of epitopes for autoantibodies to the type 1 diabetes autoantigen IA-2 by peptide phage display and molecular modeling: overlap of antibody and T cell determinants. J Immunol 2004;172:4084-90. (Pubitemid 38375220)
94. Arden SD, Roep BO, Neophytou PI, Usac EF, Duinkerken G, de Vries RR, Hutton JC. Imogen 38: a novel 38-kD islet mitochondrial autoantigen recognized by T cells from a newly diagnosed type 1 diabetic patient. J Clin Invest 1996;97:551-61. (Pubitemid 26039423)
95. Honeyman MC, Cram DS, Harrison LC. Transcription factor jun-B is target of autoreactive T-cells in IDDM. Diabetes 1993;42:626-30. (Pubitemid 23097197)
96. Atkinson MA, BowmanMA, Campbell L, Darrow BL, Kaufman DL, Maclaren NK. Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. J Clin Invest 1994;94:2125-9. (Pubitemid 24348254)
97. Nagata M, Kotani R, Moriyama H, Yokono K, Roep BO, PeakmanM. Detection of autoreactive T cells in type 1 diabetes using coded autoantigens and an immunoglobulin-free cytokine ELISPOT assay: report from the fourth immunology of diabetes society T cell workshop. Ann N Y Acad Sci 2004;1037:10-5. (Pubitemid 40299736)
98. Mallone R, Nepom GT. MHC Class II tetramers and the pursuit of antigen-specific T cells: define, deviate, delete. Clin Immunol 2004;110:232-42. (Pubitemid 38402003)
99. Serreze DV, Marron MP, Dilorenzo TP. "Humanized" HLA transgenic NOD mice to identify pancreatic beta-cell autoantigens of potential clinical relevance to type 1 diabetes. Ann N Y Acad Sci 2007;1103:103-11. (Pubitemid 46791119)
100. Roep BO, Atkinson MA, van Endert PM, Gottlieb PA, Wilson SB, Sachs JA. Autoreactive T cell responses in insulin-dependent (Type 1) diabetes mellitus. Report of the first international workshop for standardization of T cell assays. J Autoimmun 1999;13:267-82. (Pubitemid 29436141)
101. Mallone R, Nepom GT. Targeting T lymphocytes for immune monitoring and intervention in autoimmune diabetes. Am J Ther 2005;12:534-50. (Pubitemid 41689754)
102. Arif S, Tree TI, Astill TP, Tremble JM, Bishop AJ, Dayan CM, Roep BO, Peakman M. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J Clin Invest 2004;113:451-63. (Pubitemid 38544189)
103. Martinuzzi E, Novelli G, Scotto M, Blancou P, Bach JM, Chaillous L, Bruno G, Chatenoud L, van Endert P, Mallone R. The frequency and immunodominance of islet-specific CD8+ T-cell responses change after type 1 diabetes diagnosis and treatment. Diabetes 2008;57: 1312-20.
104. Shevach EM. From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 2006;25:195-201. (Pubitemid 44224153)
105. Chentoufi AA, Binder NR, Berka N, Abunadi T, Polychronakos C. Advances in type I diabetes associated tolerance mechanisms. Scand J Immunol 2008;68:1-11. (Pubitemid 351798404)
106. Lacy PE, Davie JM, Finke EH. Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS. Science 1979;204:312-3. (Pubitemid 9159646)
107. Steinman RM. Dendritic cells: understanding immunogenicity. Eur J Immunol 37 Suppl 2007;1:S53-60. (Pubitemid 350131268)
108. Gepts W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 1965;14:619-33.
109. Tisch R, Wang B. Role of plasmacytoid dendritic cells in type 1 diabetes: friend or foe? Diabetes 2009;58:12-3.
110. Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol 2009;5:219-26.
111. Dustin ML. T-cell activation through immunological synapses and kinapses. Immunol Rev 2008;221:77-89. (Pubitemid 351230116)
112. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, Julier C, Morahan G, Nerup J, Nierras C, Plagnol V, Pociot F, Schuilenburg H, Smyth DJ, Stevens H, Todd JA, Walker NM, Rich SS. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Gene, 2009.
113. Rich SS, Onengut-Gumuscu S, Concannon P. Recent progress in the genetics of diabetes. Horm Res 71 Suppl 2009;1:17-23.
114. Rich SS, Akolkar B, Concannon P, Erlich H, Hilner J, Julier C, Morahan G, Nerup J, Nierras C, Pociot F, Todd JA. Results of the MHC fine mapping workshop. Diabetes Obes Metab 11 Suppl 2009;1:108-9.
115. Sanjeevi CB, Lybrand TP, DeWeese C, Landin-Olsson M, Kockum I, Dahlquist G, Sundkvist G, Stenger D, Lernmark A. Polymorphic amino acid variations in HLA-DQ are associated with systematic physical property changes and occurrence of IDDM. Members of the Swedish Childhood Diabetes Study. Diabetes 1995;44:125-31.
116. Graham J, Kockum I, Sanjeevi CB, Landin-Olsson M, Nystrom L, Sundkvist G, Arnqvist H, Blohme G, Lithner F, Littorin B, Schersten B, Wibell L, Ostman J, Lernmark A, Breslow N, Dahlquist G. Negative association between type 1 diabetes and HLA DQB1*0602- DQA1*0102 is attenuated with age at onset. Swedish Childhood Diabetes Study Group. Eur J Immunogenet 1999;26:117-27. (Pubitemid 29195351)
117. Gillespie KM, Bain SC, Barnett AH, Bingley PJ, Christie MR, Gill GV, Gale EA. The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes. Lancet 2004;364:1699-700. (Pubitemid 39458146)
118. Resic-Lindehammer S, Larsson K, Ortqvist E, Carlsson A, Cederwall E, Cilio CM, Ivarsson SA, Jonsson BA, Larsson HE, Lynch K, Neiderud J, Nilsson A, Sjoblad S, Lernmark A, Aili M, Baath LE, Carlsson E, Edenwall H, Forsander G, Granstro BW, Gustavsson I, Hanas R, Hellenberg L, Hellgren H, Holmberg E, Hornell H, Johansson C, Jonsell G, Kockum K, Lindblad B, Lindh A, Ludvigsson J, Myrdal U, Segnestam K, Skogsberg L, Stromberg L, Stahle U, Thalme B, Tullus K, Tuvemo T, Wallensteen M, Westphal O, Aman J. Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk. Acta Diabetol 2008;45:231-35.
119. Vehik K, Hamman RF, Lezotte D, Norris JM, Klingensmith GJ, Rewers M, Dabelea D. Trends in high-risk HLA susceptibility genes among Colorado youth with type 1 diabetes. Diabetes Care 31:1392-1396. Epub 2008 Mar 2008;1320.
120. Graham J, HagopianWA, Kockum I, Li LS, Sanjeevi CB, Lowe RM, Schaefer JB, Zarghami M, Day HL, Landin-Olsson M, Palmer JP, Janer-Villanueva M, Hood L, Sundkvist G, Lernmark A, Breslow N, Dahlquist G, Blohme G. Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes. Diabetes 2002;51:1346-55. (Pubitemid 34826598)
121. Rolandsson O, Hagg E, Janer M, Rutledge E, Gaur LK, Nilsson M, Hallmans G, Lernmark A. High GAD65 autoantibody levels in nondiabetic adults are associated with HLA but not with CTLA-4 or INS VNTR. J Intern Med 2003;253:447-53. (Pubitemid 36418930)
122. Herr M, Dudbridge F, Zavattari P, Cucca F, Guja C, March R, Campbell RD, Barnett AH, Bain SC, Todd JA, Koeleman BP. Evaluation of fine mapping strategies for a multifactorial disease locus: systematic linkage and association analysis of IDDM1 in the HLA region on chromosome 6p21. Hum Mol Genet 2000;9:1291-301. (Pubitemid 30312478)
123. Vang T, Miletic AV, Bottini N, Mustelin T. Protein tyrosine phosphatase PTPN22 in human autoimmunity. Autoimmunity 2007;40:453-61. (Pubitemid 47343357)
124. Hermann R, Lipponen K, Kiviniemi M, Kakko T, Veijola R, Simell O, Knip M, Ilonen J. Lymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to type 1 diabetes. Diabetologia 2006;49:1198-208. Epub 2006 Apr 1114.
125. Steck AK, Liu SY, McFann K, Barriga KJ, Babu SR, Eisenbarth GS, Rewers MJ, She JX. Association of the PTPN22/LYP gene with type 1 diabetes. Pediatr Diabetes 2006;7:274-78. (Pubitemid 44593928)
126. Takase H, Yu CR, Mahdi RM, Douek DC, Dirusso GB, Midgley FM, Dogra R, Allende G, Rosenkranz E, Pugliese A, Egwuagu CE, Gery I. Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals. Int Immunol 2005;17:1131-1140. Epub 2005 Jul;1119. (Pubitemid 41158394)
127. Freudenthal PS, Steinman RM. The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci U S A 1990;87:7698-702. (Pubitemid 20341784)
128. Starr TK, Jameson SC, Hogquist KA. Positive and negative selection of T cells. Annu Rev Immunol 2003;21:139-76. (Pubitemid 37174529)
129. Venanzi ES, Benoist C, Mathis D. Good riddance: Thymocyte clonal deletion prevents autoimmunity. Curr Opin Immunol 2004;16:197-202. (Pubitemid 38328720)
130. Bouneaud C, Kourilsky P, Bousso P. Impact of negative selection on the T cell repertoire reactive to a self-peptide: a large fraction of T cell clones escapes clonal deletion. Immunity 2000;13:829-40. (Pubitemid 32041805)
131. Mathis D, Benoist C. Aire. Annu Rev Immunol 2009;27:287-312.
132. Derbinski J, Gabler J, Brors B, Tierling S, Jonnakuty S, Hergenhahn M, Peltonen L, Walter J, Kyewski B. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J Exp Med 2005;202:33-45. (Pubitemid 41002908)
133. Maier LM, Wicker LS. Genetic susceptibility to type 1 diabetes. Curr Opin Immunol 2005;17:601-08. (Pubitemid 41506904)
134. Onengut-Gumuscu S, Concannon P. Recent advances in the immunogenetics of human type 1 diabetes. Curr Opin Immunol 2006;18:634-8. (Pubitemid 44311456)
135. Pugliese A, Zeller M, Fernandez A, Jr., Zalcberg LJ, Bartlett RJ, Ricordi C, Pietropaolo M, Eisenbarth GS, Bennett ST, Patel DD. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet 1997;15:293-7. (Pubitemid 27098726)
136. Vafiadis P, Bennett ST, Todd JA, Nadeau J, Grabs R, Goodyer CG, Wickramasinghe S, Colle E, Polychronakos C. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nat Genet 1997;15:289-92. (Pubitemid 27098725)
137. Pugliese A, Brown D, Garza D, Murchison D, Zeller M, Redondo MJ, Diez J, Eisenbarth GS, Patel DD, Ricordi C. Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. J Clin Invest 2001;107:555-64. (Pubitemid 32205177)
138. Gotter J, Kyewski B. Regulating self-tolerance by deregulating gene expression. Curr Opin Immunol 2004;16:741-5. (Pubitemid 39423663)
139. Diez J, Park Y, Zeller M, Brown D, Garza D, Ricordi C, Hutton J, Eisenbarth GS, Pugliese A. Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a permissive genetic mechanism for autoimmunity against the IA-2 type 1 diabetes autoantigen. Diabetes 2001;50:895-900. (Pubitemid 32242651)
140. Lieberman SM, DiLorenzo TP. A comprehensive guide to antibody and T-cell responses in type 1 diabetes. Tissue Antigens 2003;62:359-77. (Pubitemid 37338877)
141. Bottini N, Vang T, Cucca F, Mustelin T. Role of PTPN22 in type 1 diabetes and other autoimmune diseases. Semin Immunol 2006;18:207-13. (Pubitemid 43903283)
142. Bennett SR, Carbone FR, Karamalis F, Flavell RA, Miller JF, HeathWR. Help for cytotoxic- T-cell responses is mediated by CD40 signalling. Nature 1998;393:478-80.
143. Linsley PS, Ledbetter JA. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol 1993;11:191-12.
144. Hernandez J, Aung S, Redmond WL, Sherman LA. Phenotypic and functional analysis of CD8(+) T cells undergoing peripheral deletion in response to cross-presentation of selfantigen. J Exp Med 2001;194:707-17. (Pubitemid 32983008)
145. Mueller DL. E3 ubiquitin ligases as T cell anergy factors. Nat Immunol 2004;5:883-90. (Pubitemid 39276232)
146. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995;182:459-65.
147. Walunas TL, Bakker CY, Bluestone JA. CTLA-4 ligation blocks CD28-dependent T cell activation. J Exp Med 1996;183:2541-50. (Pubitemid 26192364)
148. Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol 2007;19:813-24. (Pubitemid 47241890)
149. Kristiansen OP, Larsen ZM, Pociot F. CTLA-4 in autoimmune diseases - a general susceptibility gene to autoimmunity? Genes Immun 2000;1:170-84.
150. Soumelis V, Liu YJ. From plasmacytoid to dendritic cell: morphological and functional switches during plasmacytoid pre-dendritic cell differentiation. Eur J Immunol 2006;36:2286-92. (Pubitemid 44420583)
151. Liu YJ. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol 2005;23:275-306.
152. Garcia CA, Prabakar KR, Diez J, Cao ZA, Allende G, Zeller M, Dogra R, Mendez A, Rosenkranz E, Dahl U, Ricordi C, Hanahan D, Pugliese A. Dendritic cells in human thymus and periphery display a proinsulin epitope in a transcription-dependent, capture-independent fashion. J Immunol 2005;175:2111-22. (Pubitemid 41113816)
153. Rock KL, Shen L. Cross-presentation: underlying mechanisms and role in immune surveillance. Immunol Rev 2005;207:166-83. (Pubitemid 41415016)
154. Heath WR, Carbone FR. Cross-presentation, dendritic cells, tolerance and
155. Morgan DJ, Kreuwel HT, Sherman LA. Antigen concentration and precursor frequency determine the rate of CD8+ T cell tolerance to peripherally expressed antigens. J Immunol 1999;163:723-7. (Pubitemid 29328078)
156. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767-811. (Pubitemid 30365397)
157. Sen P, Bhattacharyya S, Wallet M, Wong CP, Poligone B, Sen M, Baldwin AS, Jr., Tisch R. NF-kappa B hyperactivation has differential effects on the APC function of nonobese diabetic mouse macrophages. J Immunol 2003;170:1770-80. (Pubitemid 36197392)
158. Wallet MA, Sen P, Tisch R. Immunoregulation of dendritic cells. Clin Med Res 2005;3: 166-75.
159. Rutella S, Danese S, Leone G. Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 2006;108:1435-40. (Pubitemid 44316106)
160. Yamazaki S, Inaba K, Tarbell KV, Steinman RM. Dendritic cells expand antigen-specific Foxp3+ CD25+ CD4+ regulatory T cells including suppressors of alloreactivity. Immunol Rev 2006;212:314-29. (Pubitemid 44116717)
161. Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004;4:762-74. (Pubitemid 39336293)
162. Hochweller K, Anderton SM. Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tolerance versus immunity in vivo. Eur J Immunol 2005;35:1086-96. (Pubitemid 40542215)
163. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008;26:677-704. (Pubitemid 351600389)
164. Banga JP, Moore JK, Duhindan N, Madec AM, van Endert PM, Orgiazzi J, Endl J. Modulation of antigen presentation by autoreactive B cell clones specific for GAD65 from a type I diabetic patient. Clin Exp Immunol 2004;135:74-84. (Pubitemid 38067930)
165. Reijonen H, Daniels TL, Lernmark A, Nepom GT. GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65. Diabetes 2000;49:1621-6.
166. Serreze DV, Fleming SA, Chapman HD, Richard SD, Leiter EH, Tisch RM. B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Immunol 1998;161:3912-8. (Pubitemid 28468965)
167. Tian J, Zekzer D, Lu Y, Dang H, Kaufman DL. B cells are crucial for determinant spreading of T cell autoimmunity among beta-cell antigens in diabetes-prone nonobese diabetic mice. J Immunol 2006;176:2654-61. (Pubitemid 43201718)
168. Amigorena S, Bonnerot C. Role of B-cell and Fc receptors in the selection of T-cell epitopes. Curr Opin Immunol 1998;10:88-92. (Pubitemid 28112085)
169. Jaume JC, Parry SL, Madec AM, Sonderstrup G, Baekkeskov S. Suppressive effect of glutamic acid decarboxylase 65-specific autoimmune B lymphocytes on processing of T cell determinants located within the antibody epitope. J Immunol 2002;169:665-72. (Pubitemid 34753421)
170. Fenalti G, Hampe CS, Arafat Y, Law RH, Banga JP, Mackay IR, Whisstock JC, Buckle AM, Rowley MJ. COOH-terminal clustering of autoantibody and T-cell determinants on the structure of GAD65 provide insights into the molecular basis of autoreactivity. Diabetes 2008;57:1293-301.
171. Weenink SM, Lo J, Stephenson CR, McKinney PA, Ananieva-Jordanova R, Rees Smith B, Furmaniak J, Tremble JM, Bodansky HJ, Christie MR. Autoantibodies and associated T-cell responses to determinants within the 831-860 region of the autoantigen IA-2 in Type 1 diabetes. J Autoimmun 2009.
172. Dufour FD, Silveira PA, Baxter AG. Interactions between B-lymphocytes and type 1 NKT cells in autoimmune diabetes. J Immunotoxicol 2008;5:249-57. (Pubitemid 351882413)
173. Hanninen A, Jalkanen S, Salmi M, Toikkanen S, Nikolakaros G, Simell O. Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulindependent diabetes mellitus. J Clin Invest 1992;90:1901-10.
174. Greening JE, Tree TI, Kotowicz KT, van Halteren AG, Roep BO, Klein NJ, Peakman M. Processing and presentation of the islet autoantigen GAD by vascular endothelial cells promotes transmigration of autoreactive T-cells. Diabetes 2003;52:717-25. (Pubitemid 36323579)
175. Savage CO, Brooks CJ, Harcourt GC, Picard JK, King W, Sansom DM, Willcox N. Human vascular endothelial cells process and present autoantigen to human T cell lines. Int Immunol 1995;7:471-9.
176. Savinov AY, Wong FS, Stonebraker AC, Chervonsky AV. Presentation of antigen by endothelial cells and chemoattraction are required for homing of insulin-specific CD8+ T cells. J Exp Med 2003;197:643-56. (Pubitemid 36314659)
177. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004;22:531-62. (Pubitemid 38680433)
178. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol 2008;9:239-44. (Pubitemid 351267321)
179. Ziegler SF. FOXP3: of mice and men. Annu Rev Immunol 2006;24:209-26.
180. Gambineri E, Torgerson TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol 2003;15:430-5. (Pubitemid 36774255)
181. Zhou X, Bailey-Bucktrout S, Jeker LT, Bluestone JA. Plasticity of CD4(+) FoxP3(+) T cells. Curr Opin Immunol 2009;21:281-5.
182. Hill JA, Feuerer M, Tash K, Haxhinasto S, Perez J, Melamed R, Mathis D, Benoist C. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 2007;27:786-800. (Pubitemid 350110546)
183. Lowe CE, Cooper JD, Brusko T, Walker NM, Smyth DJ, Bailey R, Bourget K, Plagnol V, Field S, Atkinson M, Clayton DG, Wicker LS, Todd JA. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet 2007;39:1074-82. (Pubitemid 47340651)
184. Bach JF. Regulatory T cells under scrutiny. Nat Rev Immunol 2003;3:189-98. (Pubitemid 37323204)
185. Chen Z, Herman AE, Matos M, Mathis D, Benoist C. Where CD4+CD25+ T reg cells impinge on autoimmune diabetes. J Exp Med 2005;202:1387-97. (Pubitemid 41668741)
186. Pop SM, Wong CP, Culton DA, Clarke SH, Tisch R. Single cell analysis shows decreasing FoxP3 and TGFbeta1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetes. J Exp Med 2005;201:1333-46. (Pubitemid 40629075)
187. Tisch R, Wang B. Dysrulation of T cell peripheral tolerance in type 1 diabetes. Adv Immunol 2008;100:125-49.
188. Roncarolo MG, Gregori S, Battaglia M, Bacchetta R, Fleischhauer K, Levings MK. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev 2006;212:28-50. (Pubitemid 44116698)
189. Moore KW, deWaal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin- 10 receptor. Annu Rev Immunol 2001;19:683-765.
190. Bhattacharyya S, Sen P, Wallet M, Long B, Baldwin AS, Jr., Tisch R. Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IkappaB kinase activity. Blood 2004;104:1100-109. (Pubitemid 39038031)
191. Vieira PL, Christensen JR, Minaee S, O'Neill EJ, Barrat FJ, Boonstra A, Barthlott T, Stockinger B, Wraith DC, O'Garra A. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J Immunol 2004;172:5986-93. (Pubitemid 38621199)
192. Shlomchik MJ. Sites and stages of autoreactive B cell activation and regulation. Immunity 2008;28:18-28.
193. Wardemann H, Nussenzweig MC. B-cell self-tolerance in humans. Adv Immunol 2007;95:83-110. (Pubitemid 47381589)
194. Verkoczy LK, Martensson AS, Nemazee D. The scope of receptor editing and its association with autoimmunity. Curr Opin Immunol 2004;16:808-14. (Pubitemid 39423673)
195. Kaufman DL, Clare-Salzler M, Tian J, Forsthuber T, Ting GS, Robinson P, Atkinson MA, Sercarz EE, Tobin AJ, Lehmann PV. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature 1993;366:69-72. (Pubitemid 23345238)
196. Moriyama H, Abiru N, Paronen J, Sikora K, Liu E, Miao D, Devendra D, Beilke J, Gianani R, Gill RG, Eisenbarth GS. Evidence for a primary islet autoantigen (preproinsulin 1) for insulitis and diabetes in the nonobese diabetic mouse. Proc Natl Acad Sci U S A 2003;100:10376-81. (Pubitemid 37071886)
197. Hoglund P, Mintern J, Waltzinger C, Heath W, Benoist C, Mathis D. Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. J Exp Med 1999;189:331-39. (Pubitemid 29063254)
198. Horwitz MS, Ilic A, Fine C, Rodriguez E, Sarvetnick N. Presented antigen from damaged pancreatic beta-cells activates autoreactive T cells in virus-mediated autoimmune diabetes. J Clin Invest 2002;109:79-87. (Pubitemid 34052544)
199. Liadis N, Murakami K, Eweida M, Elford AR, Sheu L, Gaisano HY, Hakem R, Ohashi PS, Woo M. Caspase-3-dependent beta-cell apoptosis in the initiation of autoimmune diabetes mellitus. Mol Cell Biol 2005;25: 3620-9. (Pubitemid 40559568)
200. Lio D, Candore G, Romano GC, D'Anna C, Gervasi F, Di Lorenzo G, Modica MA, Potestio M, Caruso C. Modification of cytokine patterns in subjects bearing the HLA-B8, DR3 phenotype: implications for autoimmunity. Cytokines Cell Mol Ther 1997;3:217-24.
201. Nikolic T, Geutskens SB, van Rooijen N, Drexhage HA, Leenen PJ. Dendritic cells and macrophages are essential for the retention of lymphocytes in (peri)-insulitis of the nonobese diabetic mouse: a phagocyte depletion study. Lab Invest 2005;85:487-501. (Pubitemid 40523941)
202. Bieg S, Simonson W, Ellefsen K, Lernmark A. Rel B is an early marker of autoimmune islet inflammation in the biobreeding (BB) rat. Pancreas 2000;20:47-54. (Pubitemid 30022643)
203. Lernmark A, Kloppel G, Stenger D, Vathanaprida C, Falt K, Landin-Olsson M, Baskin DG, Palmer JP, Gown AM, Petersen JS, et al. Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus. Virchows Arch 1995;425:631-40.
204. Turley S, Poirot L, Hattori M, Benoist C, Mathis D. Physiological beta-cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J Exp Med 2003;198:1527-37. (Pubitemid 37467167)
205. Zhang Y, O'Brien B, Trudeau J, Tan R, Santamaria P, Dutz JP. In situ beta-cell death promotes priming of diabetogenic CD8 T lymphocytes. J Immunol 2002;168:1466-72. (Pubitemid 34094520)
206. Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998;392:86-9 (Pubitemid 28150594)
207. Ohashi PS, Oehen S, Buerki K, Pircher H, Ohashi CT, Odermatt B, Malissen B, Zinkernagel RM, Hengartner H. Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 1991;65:305-17. (Pubitemid 121006060)
208. Oldstone MB. Molecular and cellular mechanisms, pathogenesis, and treatment of insulindependent diabetes obtained through study of a transgenic model of molecular mimicry. Curr Top Microbiol Immunol 2005;296:65-87. (Pubitemid 41667262)
209. Jun HS, Yoon JW. A new look at viruses in type 1 diabetes. Diabetes Metab Res Rev 2003;19:8-31.
210. Lipman TH, Chang Y, Murphy KM. The epidemiology of type 1 diabetes in children in Philadelphia 1990-1994: evidence of an epidemic. Diabetes Care 2002;25:1969-75. (Pubitemid 41071053)
211. Haverkos HW, Battula N, Drotman DP, Rennert OM. Enteroviruses and type 1 diabetes mellitus. Biomed Pharmacother 2003;57:379-85. (Pubitemid 37494713)
212. Hultcrantz M, Huhn MH, Wolf M, Olsson A, Jacobson S, Williams BR, Korsgren O, Flodstrom-Tullberg M. Interferons induce an antiviral state in human pancreatic islet cells. Virology 2007;367:92-101. (Pubitemid 47418925)
213. Thomas HE, Parker JL, Schreiber RD, Kay TW. IFN-gamma action on pancreatic beta-cells causes class I MHC upregulation but not diabetes. J Clin Invest 1998;102:1249-57. (Pubitemid 28436285)
214. Honeyman MC, Stone NL, Harrison LC. T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents. Mol Med 1998;4:231-9. (Pubitemid 28331640)
215. Karounos DG, Wolinsky JS, Thomas JW. Monoclonal antibody to rubella virus capsid protein recognizes a beta-cell antigen. J Immunol 1993;150:3080-5. (Pubitemid 23127557)
216. Filippi CM, von Herrath MG. Viral trigger for type 1 diabetes: pros and cons. Diabetes 2008;57:2863-71.
217. Horwitz MS, Bradley LM, Harbertson J, Krahl T, Lee J, Sarvetnick N. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med 1998;4:781-5. (Pubitemid 28331018)
218. Dotta F, Censini S, van Halteren AG, Marselli L, Masini M, Dionisi S, Mosca F, Boggi U, Muda AO, Prato SD, Elliott JF, Covacci A, Rappuoli R, Roep BO, Marchetti P. Coxsackie B4 virus infection of beta-cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci U S A 2007;104:5115-20. (Pubitemid 47186185)
219. Hou J, Sheikh S, Martin DL, Chatterjee NK. Coxsackievirus B4 alters pancreatic glutamate decarboxylase expression in mice soon after infection. J Autoimmun 1993;6:529-42.
220. Gerling I, Chatterjee NK, Nejman C. Coxsackievirus B4-induced development of antibodies to 64, 000-Mr islet autoantigen and hyperglycemia in mice. Autoimmunity 1991;10:49-56.
221. Hagopian WA, Lernmark A, Rewers MJ, Simell OG, She JX, Ziegler AG, Krischer JP, Akolkar B. TEDDY - The Environmental Determinants of Diabetes in the Young. an observational clinical trial. Ann N Y Acad Sci 2006;1079:320-6. (Pubitemid 44968741)
222. TEDDY. The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes 2007;8:286-98.
223. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008;51:216-226. Epub 2007 Dec 2018.
224. Wilson GL, Leiter EH. Streptozotocin interactions with pancreatic beta-cells and the induction of insulin-dependent diabetes. Curr Top Microbiol Immunol 1990;156:27-54. (Pubitemid 20128709)
225. Esposti MD, Ngo A, Myers MA. Inhibition of mitochondrial complex I may account for IDDM induced by intoxication with the rodenticide Vacor. Diabetes 1996;45:1531-4. (Pubitemid 26357545)
226. Myers MA, Hettiarachchi KD, Ludeman JP, Wilson AJ, Wilson CR, Zimmet PZ. Dietary microbial toxins and type 1 diabetes. Ann N Y Acad Sci 2003;1005:418-22. (Pubitemid 38507798)
227. Dahlquist GG, Blom LG, Persson L-Å, Sandström AIM, SGIW. Dietary factors and the risk of developing insulin dependent diabetes in childhood. BMJ 1990;300:1302-6. (Pubitemid 20164760)
228. Lukic ML, Stosic-Grujicic S, Shahin A. Effector mechanisms in low-dose streptozotocininduced diabetes. Dev Immunol 1998;6:119-28. (Pubitemid 28409872)
229. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 2001;50:537-46. (Pubitemid 34087272)
230. Waldrop MA, Suckow AT, Marcovina SM, Chessler SD. Release of glutamate decarboxylase-65 into the circulation by injured pancreatic islet beta-cells. Endocrinology 2007;148:4572-8. (Pubitemid 47481501)
231. Lampeter EF, Tubes M, Klemens C, Brocker U, Friemann J, Kolb-Bachofen V, Gries FA, Kolb H. Insulitis and islet-cell antibody formation in rats with experimentally reduced betacell mass. Diabetologia 1995;38:1397-404.
232. Nobile C, Lind M, Miro F, Chemin K, Tourret M, Occhipinti G, Dogniaux S, Amigorena S, Hivroz C. Cognate CD4+ T-cell-dendritic cell interactions induce migration of immature dendritic cells through dissolution of their podosomes. Blood 2008;111:3579-90.
233. Fox CJ, Danska JS. IL-4 expression at the onset of islet inflammation predicts nondestructive insulitis in nonobese diabetic mice. J Immunol 1997;158:2414-24. (Pubitemid 127470029)
234. Rabinovitch A. Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Therapeutic intervention by immunostimulation? Diabetes 1994;43:613-21. (Pubitemid 24138771)
235. Gutcher I, Becher B. APC-derived cytokines and T cell polarization in autoimmune inflammation. J Clin Invest 2007;117:1119-27. (Pubitemid 46718396)
236. Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of T(H)17 cells. Nature 2008;453:1051-7. (Pubitemid 351871737)
237. Jain R, Tartar DM, Gregg RK, Divekar RD, Bell JJ, Lee HH, Yu P, Ellis JS, Hoeman CM, Franklin CL, Zaghouani H. Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production. J Exp Med 2008;205:207-18. (Pubitemid 351185727)
238. Delon J, Germain RN. Information transfer at the immunological synapse. Curr Biol 2000;10:R923-33. (Pubitemid 32062654)
239. Grewal IS, Flavell RA. CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 1998;16:111-35. (Pubitemid 28183361)
240. Christianson SW, Shultz LD, Leiter EH. Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD. NON-Thy-1a donors. Diabetes 1993;42:44-55. (Pubitemid 23013794)
241. Graser RT, DiLorenzo TP, Wang F, Christianson GJ, Chapman HD, Roopenian DC, Nathenson SG, Serreze DV. Identification of a CD8 T cell that can independently mediate autoimmune diabetes development in the complete absence of CD4 T cell helper functions. J Immunol 2000;164:3913-8. (Pubitemid 30169851)
242. Parker DC. T cell-dependent B cell activation. Annu Rev Immunol 1993;11:331-60. (Pubitemid 23115011)
243. von Andrian UH, Mackay CR. T-cell function and migration. Two sides of the same coin. N Engl J Med 2000;343:1020-34.
244. Daniel D, Gill RG, Schloot N, Wegmann D. Epitope specificity, cytokine production profile and diabetogenic activity of insulin-specific T cell clones isolated from NOD mice. Eur J Immunol 1995;25:1056-62.
245. Wong FS, Karttunen J, Dumont C, Wen L, Visintin I, Pilip IM, Shastri N, Pamer EG, Janeway CA, Jr.: Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library. Nat Med 1999;5:1026-31. (Pubitemid 29439573)
246. Sibley RK, Sutherland DE, Goetz F, Michael AF. Recurrent diabetes mellitus in the pancreas iso- and allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab Invest 1985;53:132-44. (Pubitemid 15049005)
247. Dudda JC, Martin SF. Tissue targeting of T cells by DCs and microenvironments. Trends Immunol 2004;25:417-21. (Pubitemid 38951082)
248. Viglietta V, Kent SC, Orban T, Hafler DA. GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes. J Clin Invest 2002;109:895-903. (Pubitemid 34275110)
249. Yamanouchi J, Verdaguer J, Han B, Amrani A, Serra P, Santamaria P. Cross-priming of diabetogenic T cells dissociated from CTL-induced shedding of beta-cell autoantigens. J Immunol 2003;171:6900-9. (Pubitemid 37532126)
250. Foulis AK, Farquharson MA, Hardman R. Aberrant expression of class II major histocompatibility complex molecules by B cells and hyperexpression of class I major histocompatibility complex molecules by insulin containing islets in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1987;30:333-43. (Pubitemid 17083703)
251. Imagawa A, Hanafusa T, Tamura S, Moriwaki M, Itoh N, Yamamoto K, Iwahashi H, Yamagata K, Waguri M, Nanmo T, Uno S, Nakajima H, Namba M, Kawata S, Miyagawa JI, Matsuzawa Y. Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity. Diabetes 2001;50:1269-73. (Pubitemid 32500158)
252. Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic betacell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes 2005;54 Suppl 2:S97-107. (Pubitemid 43343337)
253. Wong FS, Visintin I, Wen L, Flavell RA, Janeway CA, Jr.: CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells. J Exp Med 1996;183:67-76. (Pubitemid 26028746)
254. Cardozo AK, Proost P, Gysemans C, Chen MC, Mathieu C, Eizirik DL. IL-1beta and IFNgamma induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice. Diabetologia 2003;46:255-66. (Pubitemid 36343890)
255. Chen MC, Proost P, Gysemans C, Mathieu C, Eizirik DL. Monocyte chemoattractant protein-1 is expressed in pancreatic islets from prediabetic NOD mice and in interleukin-1 beta-exposed human and rat islet cells. Diabetologia 2001;44:325-32. (Pubitemid 32234459)
256. Uno S, Imagawa A, Okita K, Sayama K, Moriwaki M, Iwahashi H, Yamagata K, Tamura S, Matsuzawa Y, Hanafusa T, Miyagawa J, Shimomura I. Macrophages and dendritic cells infiltrating islets with or without beta-cells produce tumour necrosis factor-alpha in patients with recent-onset type 1 diabetes. Diabetologia 2007;50:596-601. (Pubitemid 46215503)
257. Frigerio S, Junt T, Lu B, Gerard C, Zumsteg U, Hollander GA, Piali L. Beta-cells are responsible for CXCR3-mediated T-cell infiltration in insulitis. Nat Med 2002;8:1414-20. (Pubitemid 36024137)
258. Ejrnaes M, Videbaek N, Christen U, Cooke A, Michelsen BK, von Herrath M. Different diabetogenic potential of autoaggressive CD8+ clones associated with IFN-gamma-inducible protein 10 (CXC chemokine ligand 10) production but not cytokine expression, cytolytic activity, or homing characteristics. J Immunol 2005;174:2746-55. (Pubitemid 40279690)
259. McMurray RW. Adhesion molecules in autoimmune disease. Semin Arthritis Rheum 1996;25:215-33. (Pubitemid 26078481)
260. Baron JL, Reich EP, Visintin I, Janeway CA, Jr. The pathogenesis of adoptivemurine autoimmune diabetes requires an interaction between alpha 4-integrins and vascular cell adhesion molecule-1. J Clin Invest 1994;93:1700-8. (Pubitemid 24116411)
261. Fabien N, Bergerot I, Orgiazzi J, Thivolet C. Lymphocyte function associated antigen-1, integrin alpha 4, and L-selectin mediate T-cell homing to the pancreas in the model of adoptive transfer of diabetes in NOD mice. Diabetes 1996;45:1181-6. (Pubitemid 26296316)
262. Somoza N, Vargas F, Roura-Mir C, Vives-Pi M, Fernandez-Figueras MT, Ariza A, Gomis R, Bragado R, Marti M, Jaraquemada D, et al.: Pancreas in recent onset insulin-dependent diabetes mellitus. Changes in HLA, adhesion molecules and autoantigens, restricted T cell receptor V beta usage, and cytokine profile. J Immunol 1994;153:1360-77. (Pubitemid 24228529)
263. Hogg N, Leitinger B. Shape and shift changes related to the function of leukocyte integrins LFA-1 and Mac-1. J Leukoc Biol 2001;69:893-8. (Pubitemid 32577889)
264. Mobley JL, Reynolds PJ, Shimizu Y. Regulatory mechanisms underlying T cell integrin receptor function. Semin Immunol 1993;5:227-36.
265. Falcone M, Lee J, Patstone G, Yeung B, Sarvetnick N. B lymphocytes are crucial antigenpresenting cells in the pathogenic autoimmune response to GAD65 antigen in nonobese diabetic mice. J Immunol 1998;161:1163-8. (Pubitemid 28380541)
266. Martin S, Wolf-Eichbaum D, Duinkerken G, Scherbaum WA, Kolb H, Noordzij JG, Roep BO. Development of type 1 diabetes despite severe hereditary B-lymphocyte deficiency. N Engl J Med 2001;345:1036-40.
267. Dobersen MJ, Scharff JE, Ginsberg-Fellner F, Notkins AL. Cytotoxic autoantibodies to beta-cells in the serum of patients with insulin-dependent diabetes mellitus. N Engl J Med 1980;303:1493-8. (Pubitemid 11178977)
268. Hummel M, Durinovic-Bello I, Ziegler AG. Relation between cellular and humoral immunity to islet cell antigens in type 1 diabetes. J Autoimmun 1996;9:427-30. (Pubitemid 26226606)
269. Wallberg M, Green EA. Are B cells a potential target for therapeutic intervention in the classical T cell-mediated autoimmune disease type 1 diabetes? Inflamm Allergy Drug Targets 2009;8:130-8.
270. Shoenfeld Y. The idiotypic network in autoimmunity: antibodies that bind antibodies that bind antibodies. Nat Med 2004;10:17-8. (Pubitemid 38524686)
271. Kim HS, Lee MS. Role of innate immunity in triggering and tuning of autoimmune diabetes. Curr Mol Med 2009;9:30-44.
272. Lang KS, Recher M, Junt T, Navarini AA, Harris NL, Freigang S, Odermatt B, Conrad C, Ittner LM, Bauer S, Luther SA, Uematsu S, Akira S, Hengartner H, Zinkernagel RM. Tolllike receptor engagement converts T-cell autoreactivity into overt autoimmune disease. Nat Med 2005;11:138-45. (Pubitemid 40321348)
273. Millar DG, Garza KM, Odermatt B, Elford AR, Ono N, Li Z, Ohashi PS. Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo. Nat Med 2003;9:1469-76. (Pubitemid 38004773)
274. Rajagopal D, Bal V, Mayor S, George A, Rath S. A role for the Hsp90 molecular chaperone family in antigen presentation to T lymphocytes via major histocompatibility complex class II molecules. Eur J Immunol 2006;36:828-41.
275. Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 1999;285:727-9.
276. Cardell SL. The natural killer T lymphocyte: a player in the complex regulation of autoimmune diabetes in non-obese diabetic mice. Clin Exp Immunol 2006;143:194-202.
277. Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 2005;23:877-900. (Pubitemid 40563188)
278. Hammond KJ, Kronenberg M. Natural killer T cells: natural or unnatural regulators of autoimmunity? Curr Opin Immunol 2003;15:683-9. (Pubitemid 37434076)
279. Maruyama T, Watanabe K, Yanagawa T, Kasatani T, Kasuga A, Shimada A, Takei I, Suzuki Y, Kataoka K, Saruta T. The suppressive effect of anti-asialo GM1 antibody on low-dose streptozotocin-induced diabetes in CD-1 mice. Diabetes Res 1991;16:171-5.
280. Ellerman K, Wrobleski M, Rabinovitch A, Like A. Natural killer cell depletion and diabetes mellitus in the BB/Wor rat (revisited). Diabetologia 1993;36:596-601. (Pubitemid 23186450)
281. Flodstrom M, Maday A, Balakrishna D, Cleary MM, Yoshimura A, Sarvetnick N. Target cell defense prevents the development of diabetes after viral infection. Nat Immunol 2002;3:373-82. (Pubitemid 34308626)
282. Lee IF, Qin H, Trudeau J, Dutz J, Tan R. Regulation of autoimmune diabetes by complete Freund's adjuvant is mediated by NK cells. J Immunol 2004;172:937-42. (Pubitemid 38113752)
283. Novak J, Griseri T, Beaudoin L, Lehuen A. Regulation of type 1 diabetes by NKT cells. Int Rev Immunol 2007;26:49-72. (Pubitemid 46512166)
284. Chen YG, Choisy-Rossi CM, Holl TM, Chapman HD, Besra GS, Porcelli SA, Shaffer DJ, Roopenian D, Wilson SB, Serreze DV. Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes. J Immunol 2005;174:1196-1204.
285. Naumov YN, Bahjat KS, Gausling R, Abraham R, Exley MA, Koezuka Y, Balk SB, Strominger JL, Clare-Salzer M, Wilson SB. Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets. Proc Natl Acad Sci U S A 2001;98:13838-43. (Pubitemid 33115985)
286. Mi QS, Ly D, Zucker P, McGarry M, Delovitch TL. Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells. Diabetes 2004;53:1303-10. (Pubitemid 38569017)
287. Griseri T, Beaudoin L, Novak J, Mars LT, Lepault F, Liblau R, Lehuen A. Invariant NKT cells exacerbate type 1 diabetes induced by CD8 T cells. J Immunol 2005;175:2091-101. (Pubitemid 41113814)
288. Han B, Serra P, Yamanouchi J, Amrani A, Elliott JF, Dickie P, Dilorenzo TP, Santamaria P. Developmental control of CD8 T cell-avidity maturation in autoimmune diabetes. J Clin Invest 2005;115:1879-87. (Pubitemid 40979727)
289. Mathis D, Vence L, Benoist C. beta-Cell death during progression to diabetes. Nature 2001;414:792-8.
290. Skowera A, Ellis RJ, Varela-Calvino R, Arif S, Huang GC, Van-Krinks C, Zaremba A, Rackham C, Allen JS, Tree TI, Zhao M, Dayan CM, Sewell AK, Unger W, Drijfhout JW, Ossendorp F, Roep BO, Peakman M. CTLs are targeted to kill beta-cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope. J Clin Invest 2008;118:3390-402.
291. Chong MM, Chen Y, Darwiche R, Dudek NL, Irawaty W, Santamaria P, Allison J, Kay TW, Thomas HE. Suppressor of cytokine signaling-1 overexpression protects pancreatic betacells from CD8+ T cell-mediated autoimmune destruction. J Immunol 2004;172:5714-21. (Pubitemid 38542076)
292. Eizirik DL, Kutlu B, Rasschaert J, Darville M, Cardozo AK. Use of microarray analysis to unveil transcription factor and gene networks contributing to Beta cell dysfunction and apoptosis. Ann N Y Acad Sci 2003;1005:55-74. (Pubitemid 38507734)
293. Bendtzen K, Mandrup-Poulsen T, Nerup J, Nielsen JH, Dinarello CA, Svenson M. Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans. Science 1986;232:1545-7. (Pubitemid 16061563)
294. Eizirik DL, Tracey DE, Bendtzen K, Sandler S. An interleukin-1 receptor antagonist protein protects insulin-producing beta-cells against suppressive effects of interleukin-1 beta. Diabetologia 1991;34:445-8.
295. Arnush M, Heitmeier MR, Scarim AL, Marino MH, Manning PT, Corbett JA. IL-1 produced and released endogenously within human islets inhibits beta cell function. J Clin Invest 1998;102:516-26. (Pubitemid 28376154)
296. Hughes JH, Colca JR, Easom RA, Turk J, McDaniel ML. Interleukin 1 inhibits insulin secretion from isolated rat pancreatic islets by a process that requires gene transcription and mRNA translation. J Clin Invest 1990;86:856-63. (Pubitemid 20327376)
297. Southern C, Schulster D, Green IC. Inhibition of insulin secretion by interleukin-1 beta and tumour necrosis factor-alpha via an L-arginine-dependent nitric oxide generating mechanism. FEBS Lett 1990;276:42-4.
298. Thomas HE, Darwiche R, Corbett JA, Kay TW. Interleukin-1 plus gamma-interferoninduced pancreatic beta-cell dysfunction is mediated by beta-cell nitric oxide production. Diabetes 2002;51:311-6. (Pubitemid 34764785)
299. Corbett JA, Wang JL, Sweetland MA, Lancaster JR, Jr., McDaniel ML. Interleukin 1 beta induces the formation of nitric oxide by beta-cells purified from rodent islets of Langerhans. Evidence for the beta-cell as a source and site of action of nitric oxide. J Clin Invest 1992;90:2384-91. (Pubitemid 23010057)
300. Kubisch HM, Wang J, Bray TM, Phillips JP. Targeted overexpression of Cu/Zn superoxide dismutase protects pancreatic beta-cells against oxidative stress. Diabetes 1997;46:1563-6. (Pubitemid 27411230)
301. Su X, Hu Q, Kristan JM, Costa C, Shen Y, Gero D, Matis LA, Wang Y. Significant role for Fas in the pathogenesis of autoimmune diabetes. J Immunol 2000;164:2523-32. (Pubitemid 30115482)
302. Poligone B, Weaver DJ, Jr., Sen P, Baldwin AS, Jr., Tisch R. Elevated NF-kappaB activation in nonobese diabetic mouse dendritic cells results in enhanced APC function. J Immunol 2002;168:188-96. (Pubitemid 34014118)
303. Liu J, Beller DI. Distinct pathways for NF-kappa B regulation are associated with aberrant macrophage IL-12 production in lupus- and diabetes-prone mouse strains. J Immunol 2003;170:4489-96. (Pubitemid 36519954)
304. Grohmann U, Fallarino F, Bianchi R, Orabona C, Vacca C, Fioretti MC, Puccetti P. A defect in tryptophan catabolism impairs tolerance in nonobese diabetic mice. J Exp Med 2003;198:153-60. (Pubitemid 36870195)
305. Summers KL, Marleau AM, Mahon JL, McManus R, Hramiak I, Singh B. Reduced IFNalpha secretion by blood dendritic cells in human diabetes. Clin Immunol 2006;121:81-9. (Pubitemid 44380413)
306. Plesner A, Greenbaum CJ, Gaur LK, Ernst RK, Lernmark A. Macrophages from high-risk HLA-DQB1*0201/*0302 type 1 diabetes mellitus patients are hypersensitive to lipopolysaccharide stimulation. Scand J Immunol 2002;56:522-9. (Pubitemid 35373690)
307. Vuckovic S, Withers G, Harris M, Khalil D, Gardiner D, Flesch I, Tepes S, Greer R, Cowley D, Cotterill A, Hart DN. Decreased blood dendritic cell counts in type 1 diabetic children. Clin Immunol 2007;123:281-8. (Pubitemid 46818130)
308. Zacher T, Knerr I, Rascher W, Kalden JR, Wassmuth R. Characterization of monocytederived dendritic cells in recent-onset diabetes mellitus type 1. Clin Immunol 2002;105: 17-24. (Pubitemid 35222238)
309. Alard P, Manirarora JN, Parnell SA, Hudkins JL, Clark SL, Kosiewicz MM. Deficiency in NOD antigen-presenting cell function may be responsible for suboptimal CD4+CD25+ T-cell-mediated regulation and type 1 diabetes development in NOD mice. Diabetes 2006;55:2098-105. (Pubitemid 44509985)
310. Delemarre FG, Simons PJ, de Heer HJ, Drexhage HA. Signs of immaturity of splenic dendritic cells from the autoimmune prone biobreeding rat: consequences for the in vitro expansion of regulator and effector T cells. J Immunol 1999;162:1795-801. (Pubitemid 29307060)
311. Mollah ZU, Pai S, Moore C, O'Sullivan BJ, Harrison MJ, Peng J, Phillips K, Prins JB, Cardinal J, Thomas R. Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monocytes. J Immunol 2008;180:3166-75.
312. Allen JS, Pang K, Skowera A, Ellis R, Rackham C, Lozanoska-Ochser B, Tree T, Leslie RD, Tremble JM, Dayan CM, Peakman M. Plasmacytoid dendritic cells are proportionally expanded at diagnosis of type 1 diabetes and enhance islet autoantigen presentation to T-cells through immune complex capture. Diabetes 2009;58:138-45.
313. Vidard L, Rock KL, Benacerraf B. Heterogeneity in antigen processing by different types of antigen-presenting cells. Effect of cell culture on antigen processing ability. J Immunol 1992;149:1905-11.
314. Reijonen H, Elliott JF, van Endert P, Nepom G. Differential presentation of glutamic acid decarboxylase 65 (GAD65) T cell epitopes among HLA-DRB1*0401-positive individuals. J Immunol 1999;163:1674-81. (Pubitemid 29352793)
315. Osugi Y, Vuckovic S, Hart DN. Myeloid blood CD11c(+) dendritic cells and monocytederived dendritic cells differ in their ability to stimulate T lymphocytes. Blood 2002;100:2858-66.
316. Blancou P, Mallone R, Martinuzzi E, Severe S, Pogu S, Novelli G, Bruno G, Charbonnel B, Dolz M, Chaillous L, van Endert P, Bach JM. Immunization of HLA class I transgenic mice identifies autoantigenic epitopes eliciting dominant responses in type 1 diabetes patients. J Immunol 2007;178:7458-66. (Pubitemid 46847474)
317. Peakman M, Stevens EJ, Lohmann T, Narendran P, Dromey J, Alexander A, Tomlinson AJ, Trucco M, Gorga JC, Chicz RM. Naturally processed and presented epitopes of the islet cell autoantigen IA-2 eluted from HLA-DR4. J Clin Invest 1999;104:1449-57.
318. Oling V, Marttila J, Ilonen J, KwokWW, Nepom G, Knip M, Simell O, Reijonen H. GAD65- and proinsulin-specific CD4+ T-cells detected by MHC class II tetramers in peripheral blood of type 1 diabetes patients and at-risk subjects. J Autoimmun 2005;25:235-43. (Pubitemid 41654469)
319. Reijonen H, Novak EJ, Kochik S, Heninger A, Liu AW, Kwok WW, Nepom GT. Detection of GAD65-specific T-cells by major histocompatibility complex class II tetramers in type 1 diabetic patients and at-risk subjects. Diabetes 2002;51:1375-82. (Pubitemid 34826602)
320. Endl J, Otto H, Jung G, Dreisbusch B, Donie F, Stahl P, Elbracht R, Schmitz G, Meinl E, Hummel M, Ziegler AG, Wank R, Schendel DJ. Identification of naturally processed T cell epitopes from glutamic acid decarboxylase presented in the context of HLA-DR alleles by T lymphocytes of recent onset IDDM patients. J Clin Invest 1997;99:2405-15. (Pubitemid 27227718)
321. Nepom GT, Lippolis JD, White FM, Masewicz S, Marto JA, Herman A, Luckey CJ, Falk B, Shabanowitz J, Hunt DF, Engelhard VH, Nepom BS. Identification and modulation of a naturally processed T cell epitope from the diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65). Proc Natl Acad Sci U S A 2001;98:1763-8. (Pubitemid 32165572)
322. Reijonen H, Mallone R, Heninger AK, Laughlin EM, Kochik SA, Falk B, Kwok WW, Greenbaum C, Nepom GT. GAD65-specific CD4+ T-cells with high antigen avidity are prevalent in peripheral blood of patients with type 1 diabetes. Diabetes 2004;53:1987-94. (Pubitemid 38970746)
323. Mallone R, Martinuzzi E, Blancou P, Novelli G, Afonso G, Dolz M, Bruno G, Chaillous L, Chatenoud L, Bach JM, van Endert P. CD8+ T-cell responses identify beta-cell autoimmunity in human type 1 diabetes. Diabetes 2007;56:613-21. (Pubitemid 46348452)
324. Hassainya Y, Garcia-Pons F, Kratzer R, Lindo V, Greer F, Lemonnier FA, Niedermann G, van Endert PM. Identification of naturally processed HLA-A2 - restricted proinsulin epitopes by reverse immunology. Diabetes 2005;54:2053-9. (Pubitemid 40911268)
325. Pinkse GG, Tysma OH, Bergen CA, Kester MG, Ossendorp F, van Veelen PA, Keymeulen B, Pipeleers D, Drijfhout JW, Roep BO. Autoreactive CD8 T cells associated with beta-cell destruction in type 1 diabetes. Proc Natl Acad Sci U S A 2005;102:18425-30. (Pubitemid 43011242)
326. Hawkes CJ, Schloot NC, Marks J, Willemen SJ, Drijfhout JW, Mayer EK, Christie MR, Roep BO. T-cell lines reactive to an immunodominant epitope of the tyrosine phosphataselike autoantigen IA-2 in type 1 diabetes. Diabetes 2000;49:356-66. (Pubitemid 30131780)
327. Ouyang Q, Standifer NE, Qin H, Gottlieb P, Verchere CB, Nepom GT, Tan R, Panagiotopoulos C. Recognition of HLA class I-restricted beta-cell epitopes in type 1 diabetes. Diabetes 2006;55:3068-74. (Pubitemid 44923644)
328. Standifer NE, Ouyang Q, Panagiotopoulos C, Verchere CB, Tan R, Greenbaum CJ, Pihoker C, Nepom GT. Identification of Novel HLA-A*0201-restricted epitopes in recent-onset type 1 diabetic subjects and antibody-positive relatives. Diabetes 2006;55:3061-7. (Pubitemid 44923643)
329. Panagiotopoulos C, Qin H, Tan R, Verchere CB. Identification of a beta-cell-specific HLA class I restricted epitope in type 1 diabetes. Diabetes 2003;52:2647-51. (Pubitemid 37339692)
330. Di Lorenzo TP, Peakman M, Roep BO. Translational mini-review series on type 1 diabetes: Systematic analysis of T cell epitopes in autoimmune diabetes. Clin Exp Immunol 2007;148:1-16. (Pubitemid 46364983)
331. Jarchum I, Nichol L, Trucco M, Santamaria P, DiLorenzo TP. Identification of novel IGRP epitopes targeted in type 1 diabetes patients. Clin Immunol 2008;127:359-65.
332. Marttila J, Huttunen S, Vaarala O, Suzuki K, Elliott JF, Narvanen A, Knip M, Simell O, Ilonen J. T-cell reactivity to insulin peptide A1-12 in children with recently diagnosed type 1 diabetes or multiple beta-cell autoantibodies. J Autoimmun 2008;31:142-8.
333. Toma A, Laika T, Haddouk S, Luce S, Briand JP, Camoin L, Connan F, Lambert M, Caillat- Zucman S, Carel JC, Muller S, Choppin J, Lemonnier F, Boitard C. Recognition of human proinsulin leader sequence by class I-restricted T-cells in HLA-A*0201 transgenic mice and in human type 1 diabetes. Diabetes 2009;58:394-402.
334. Mannering SI, Pang SH, Williamson NA, Naselli G, Reynolds EC, O'Brien-Simpson NM, Purcell AW, Harrison LC. The A-chain of insulin is a hot-spot for CD4+ T cell epitopes in human type 1 diabetes. Clin Exp Immunol 2009;156:226-31.
335. Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 1999;50:213-9. (Pubitemid 30099526)
336. Parker KC, Bednarek MA, Coligan JE. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol 1994;152:163-75.
337. Baker C, Petrich de Marquesini LG, Bishop AJ, Hedges AJ, Dayan CM, Wong FS. Human CD8 responses to a complete epitope set from preproinsulin: implications for approaches to epitope discovery. J Clin Immunol 2008;28:350-60.
338. Danke NA, Yang J, Greenbaum C, Kwok WW. Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. J Autoimmun 2005;25:303-11. (Pubitemid 41642977)
339. Monti P, Scirpoli M, Rigamonti A, Mayr A, Jaeger A, Bonfanti R, Chiumello G, Ziegler AG, Bonifacio E. Evidence for in vivo primed and expanded autoreactive T cells as a specific feature of patients with type 1 diabetes. J Immunol 2007;179:5785-92.
340. Yang J, Danke N, Roti M, Huston L, Greenbaum C, Pihoker C, James E, Kwok WW. CD4+ T cells from type 1 diabetic and healthy subjects exhibit different thresholds of activation to a naturally processed proinsulin epitope. J Autoimmun 2008;31:30-41.
341. Tree TI, Roep BO, Peakman M. A mini meta-analysis of studies on CD4+CD25+ T cells in human type 1 diabetes: report of the Immunology of Diabetes Society T Cell Workshop. Ann N Y Acad Sci 2006;1079:9-18. (Pubitemid 44968695)
342. Brusko T, Wasserfall C, McGrail K, Schatz R, Viener HL, Schatz D, Haller M, Rockell J, Gottlieb P, Clare-Salzler M, Atkinson M. No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes. Diabetes 2007;56:604-12. (Pubitemid 46348451)
343. 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;54:92-9. (Pubitemid 40105099)
344. Gregori S, Giarratana N, Smiroldo S, Adorini L. Dynamics of pathogenic and suppressor T cells in autoimmune diabetes development. J Immunol 2003;171:4040-7. (Pubitemid 37238678)
345. You S, Belghith M, Cobbold S, Alyanakian MA, Gouarin C, Barriot S, Garcia C, Waldmann H, Bach JF, Chatenoud L. Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T-cells. Diabetes 2005;54:1415-22. (Pubitemid 40586672)
346. Korn T, Oukka M. Dynamics of antigen-specific regulatory T-cells in the context of autoimmunity. Semin Immunol 2007;19:272-8. (Pubitemid 47043483)
347. Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med 2005;201:723-35. (Pubitemid 40395118)
348. Tang Q, Adams JY, Penaranda C, Melli K, Piaggio E, Sgouroudis E, Piccirillo CA, Salomon BL, Bluestone JA. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 2008;28:687-97.
349. Gregg RK, Jain R, Schoenleber SJ, Divekar R, Bell JJ, Lee HH, Yu P, Zaghouani H. A sudden decline in active membrane-bound TGF-beta impairs both T regulatory cell function and protection against autoimmune diabetes. J Immunol 2004;173:7308-16. (Pubitemid 39628168)
350. Wu AJ, Hua H, Munson SH, McDevitt HO. Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice. Proc Natl Acad Sci U S A 2002;99:12287-92.
351. Clough LE, Wang CJ, Schmidt EM, Booth G, Hou TZ, Ryan GA, Walker LS. Release from regulatory T cell-mediated suppression during the onset of tissue-specific autoimmunity is associated with elevated IL-21. J Immunol 2008;180:5393-401.
352. Yamanouchi J, Rainbow D, Serra P, Howlett S, Hunter K, Garner VE, Gonzalez-Munoz A, Clark J, Veijola R, Cubbon R, Chen SL, Rosa R, Cumiskey AM, Serreze DV, Gregory S, Rogers J, Lyons PA, Healy B, Smink LJ, Todd JA, Peterson LB, Wicker LS, Santamaria P. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet 2007;39:329-37. (Pubitemid 46328484)
353. Sanda S, Roep BO, von Herrath M. Islet antigen specific IL-10+ immune responses but not CD4+CD25+FoxP3+ cells at diagnosis predict glycemic control in type 1 diabetes. Clin Immunol 2008;127:138-43.
354. Nicoletti F, Conget I, Di Mauro M, Di Marco R, Mazzarino MC, Bendtzen K, Messina A, Gomis R. Serum concentrations of the interferon-gamma-inducible chemokine IP- 10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease. Diabetologia 2002;45:1107-110. (Pubitemid 34985286)
355. Shimada A, Morimoto J, Kodama K, Suzuki R, Oikawa Y, Funae O, Kasuga A, Saruta T, Narumi S. Elevated serum IP-10 levels observed in type 1 diabetes. Diabetes Care 2001;24:510-5. (Pubitemid 32198422)
356. Lampeter ER, Kishimoto TK, Rothlein R, Mainolfi EA, Bertrams J, Kolb H, Martin S. Elevated levels of circulating adhesion molecules in IDDM patients and in subjects at risk for IDDM. Diabetes 1992;41:1668-71.
357. Rodacki M, Milech A, de Oliveira JE. NK cells and type 1 diabetes. Clin Dev Immunol 2006;13:101-7. (Pubitemid 44950029)
358. Lorini R, Moretta A, Valtorta A, d'Annunzio G, Cortona L, Vitali L, Bozzola M, Severi F. Cytotoxic activity in children with insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1994;23:37-42. (Pubitemid 24118513)
359. Rodacki M, Svoren B, Butty V, Besse W, Laffel L, Benoist C, Mathis D. Altered natural killer cells in type 1 diabetic patients. Diabetes 2007;56:177-85.
360. Gambelunghe G, Ghaderi M, Cosentino A, Falorni A, Brunetti P, Sanjeevi CB. Association of MHC Class I chain-related A (MIC-A) gene polymorphism with Type I diabetes. Diabetologia 2000;43:507-14. (Pubitemid 30237961)
361. Oikawa Y, Shimada A, Yamada S, Motohashi Y, Nakagawa Y, Irie J, Maruyama T, Saruta T. High frequency of valpha24(+) vbeta11(+) T-cells observed in type 1 diabetes. Diabetes Care 2002;25:1818-23. (Pubitemid 41071093)
362. Kis J, Engelmann P, Farkas K, Richman G, Eck S, Lolley J, Jalahej H, Borowiec M, Kent SC, Treszl A, Orban T. Reduced CD4+ subset and Th1 bias of the human iNKT cells in Type 1 diabetes mellitus. J Leukoc Biol 2007;81:654-62. (Pubitemid 46393543)
363. Kukreja A, Cost G, Marker J, Zhang C, Sun Z, Lin-Su K, Ten S, Sanz M, Exley M, Wilson B, Porcelli S, Maclaren N. Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest 2002;109:131-40. (Pubitemid 34052549)
364. Lee PT, Putnam A, Benlagha K, Teyton L, Gottlieb PA, Bendelac A. Testing the NKT cell hypothesis of human IDDM pathogenesis. J Clin Invest 2002;110:793-800.
365. Wong CP, Stevens R, Long B, Li L, Wang Y, Wallet MA, Goudy KS, Frelinger JA, Tisch R. Identical beta cell-specific CD8(+) T cell clonotypes typically reside in both peripheral blood lymphocyte and pancreatic islets. J Immunol 2007;178:1388-95. (Pubitemid 46154609)
366. Enee E, Martinuzzi E, Blancou P, Bach JM, Mallone R, van Endert P. Equivalent specificity of peripheral blood and islet-infiltrating CD8+ T lymphocytes in spontaneously diabetic HLA-A2 transgenic NOD mice. J Immunol 2008;180:5430-8.
367. Wang X, Jia S, Geoffrey R, Alemzadeh R, Ghosh S, Hessner MJ. Identification of a molecular signature in human type 1 diabetes mellitus using serum and functional genomics. J Immunol 2008;180:1929-37.
368. Eisenbarth GS. Prediction of type 1 diabetes: the natural history of the prediabetic period. Adv Exp Med Biol 2004;552:268-90. (Pubitemid 40090330)
369. Hagopian WA, Michelsen B, Karlsen AE, Larsen F, Moody A, Grubin CE, Rowe R, Petersen J, McEvoy R, Lernmark A. Autoantibodies in IDDM primarily recognize the 65, 000-M(r) rather than the 67, 000-M(r) isoform of glutamic acid decarboxylase. Diabetes 1993;42: 631-6. (Pubitemid 23097198)
370. Padoa CJ, Banga JP, Madec AM, Ziegler M, Schlosser M, Ortqvist E, Kockum I, Palmer J, Rolandsson O, Binder KA, Foote J, Luo D, Hampe CS. Recombinant Fabs of human monoclonal antibodies specific to the middle epitope of GAD65 inhibit type 1 diabetesspecific GAD65Abs. Diabetes 2003;52:2689-95. (Pubitemid 37339698)
371. Hampe CS, Hammerle LP, Bekris L, Ortqvist E, Kockum I, Rolandsson O, Landin-Olsson M, Torn C, Persson B, Lernmark A. Recognition of glutamic acid decarboxylase (GAD) by autoantibodies from different GAD antibody-positive phenotypes. J Clin Endocrinol Metab 2000;85:4671-9. (Pubitemid 32157650)
372. Richter W, Shi Y, Baekkeskov S. Autoreactive epitopes defined by diabetes-associated human monoclonal antibodies are localized in the middle and C-terminal domains of the smaller form of glutamate decarboxylase. Proc Natl Acad Sci U S A 1993;90:2832-6. (Pubitemid 23113511)
373. Bjork E, Velloso LA, Kampe O, Karlsson FA. GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes. Diabetes 1994;43:161-5.
374. Kobayashi T, Tanaka S, Okubo M, Nakanishi K, Murase T, Lernmark A. Unique epitopes of glutamic acid decarboxylase autoantibodies in slowly progressive type 1 diabetes. J Clin Endocrinol Metab 2003;88:4768-75. (Pubitemid 37357524)
375. Oak S, Gilliam LK, Landin-Olsson M, Torn C, Kockum I, Pennington CR, Rowley MJ, Christie MR, Banga JP, Hampe CS. The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes. Proc Natl Acad Sci U S A 2008;105:5471-6. (Pubitemid 351753887)
376. Kukko M, Kimpimaki T, Korhonen S, Kupila A, Simell S, Veijola R, Simell T, Ilonen J, Simell O, Knip M. Dynamics of diabetes-associated autoantibodies in young children with human leukocyte antigen-conferred risk of type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 2005;90:2712-17. (Pubitemid 40686314)
377. Eisenbarth GS, Moriyama H, Robles DT, Liu E, Yu L, Babu S, Redondo MJ, Gottlieb P, Wegmann D, Rewers M. Insulin autoimmunity: prediction/precipitation/ prevention type 1A diabetes. Autoimmun Rev 2002;1:139-45. (Pubitemid 38340264)
378. Brooks-Worrell BM, Nielson D, Palmer JP. Insulin autoantibodies and insulin antibodies have similar binding characteristics. Proc Assoc Am Physicians 1999;111:92-6. (Pubitemid 29047114)
379. Hatfield EC, Hawkes CJ, Payton MA, Christie MR. Cross reactivity between IA-2 and phogrin/IA-2beta in binding of autoantibodies in IDDM. Diabetologia 1997;40:1327-33. (Pubitemid 27469674)
380. Zhang B, Lan MS, Notkins AL. Autoantibodies to IA-2 in IDDM: location of major antigenic determinants. Diabetes 1997;46:40-3. (Pubitemid 27009947)
381. Endo T, Takizawa S, Tanaka S, Takahashi M, Fujii H, Kamisawa T, Kobayashi T. Amylase alpha-2A autoantibodies: novel marker of autoimmune pancreatitis and fulminant type 1 diabetes. Diabetes 2009;58:732-7.
382. Meagher C, Tang Q, Fife BT, Bour-Jordan H, Wu J, Pardoux C, Bi M, Melli K, Bluestone JA. Spontaneous development of a pancreatic exocrine disease in CD28-deficient NOD mice. J Immunol 2008;180:7793-803.
383. Baekkeskov S, Landin M, Kristensen JK, Srikanta S, Bruining GJ, Mandrup-Poulsen T, de Beaufort C, Soeldner JS, Eisenbarth G, Lindgren F, et al.: Antibodies to a 64, 000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes. J Clin Invest 1987;79:926-34. (Pubitemid 17050921)
384. Thivolet CH, Tappaz M, Durand A, Petersen J, Stefanutti A, Chatelain P, Vialettes B, Scherbaum W, Orgiazzi J. Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals. Diabetologia 1992;35:570-6.
385. Wasserfall CH, Atkinson MA. Autoantibody markers for the diagnosis and prediction of type 1 diabetes. Autoimmun Rev 2006;5:424-8. (Pubitemid 44150627)
386. Bingley PJ, Christie MR, Bonifacio E, Bonfanti R, Shattock M, Fonte MT, Bottazzo GF, Gale EA. Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes 1994;43:1304-10.
387. Verge CF, Gianani R, Kawasaki E, Yu L, Pietropaolo M, Jackson RA, Chase HP, Eisenbarth GS. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 1996;45:926-33. (Pubitemid 26225509)
388. In't Veld P, Lievens D, De Grijse J, Ling Z, Van der Auwera B, Pipeleers-Marichal M, Gorus F, Pipeleers D. Screening for insulitis in adult autoantibody-positive organ donors. Diabetes 2007;56:2400-4. (Pubitemid 47358248)
389. Skarsvik S, Tiittanen M, Lindstrom A, Casas R, Ludvigsson J, Vaarala O. Poor in vitro maturation and pro-inflammatory cytokine response of dendritic cells in children at genetic risk of type 1 diabetes. Scand J Immunol 2004;60:647-52. (Pubitemid 39665111)
390. Takahashi K, Honeyman MC, Harrison LC. Impaired yield, phenotype, and function of monocyte-derived dendritic cells in humans at risk for insulin-dependent diabetes. J Immunol 1998;161:2629-35. (Pubitemid 28397083)