Autoimmune Diabetes: The Role of T Cells, MHC Molecules and Autoantigens

References

• Liblau R. S., Singer S. M., McDevitt H. O. Thl and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol. Today 1995; 16: 34–8
   PubMedGoogle Scholar
• Scott P. Selective differentiation of CD4+ T-helper cell subsets. Curr Opin Immunol 1993; 5: 391–7
   PubMedGoogle Scholar
• Zinkernagel R. M. Immunology taught by viruses. Science 1996; 271: 173–8
   PubMed Web of Science ®Google Scholar
• Mandrup-Poulsen T. The role of interleukin-1 in the pathogenesis of IDDM. Diabelologia 1996; 39: 1005–29
   PubMed Web of Science ®Google Scholar
• Naquet P., Ellis J., Tibensky D., Kenshole A., Singh B., Hodges R., et al. T cell autoreactivity to insulin in diabetic and related non-diabetic individuals. J. Immunol. 1988; 140: 2569–78
   PubMedGoogle Scholar
• Harrison L. C, Chu S. X., DeAizpurua H. J., Graham M., Honeyman M. C., Colman P. G. Islet-reactive T cells are a marker of preclinical insulin-dependent diabetes. J. Clin. Invest. 1992; 89: 1161–5
   PubMedGoogle Scholar
• Roep B. O. T-cell responses to autoantigens in IDDM. The search for the Holy Grail. Diabetes 1996; 45: 1147–56
   PubMed Web of Science ®Google Scholar
• Durinovic Bello I., Steinle A., Ziegler A. G., Schen-Del D. J. HLA-DQ-restricted, islet-specihc T-cell clones of a type I diabetic patient. T-cell receptor sequence similarities to insulitis-inducing T-cells of nonobese diabetic mice. Diabetes 1994; 43: 1318–25
   PubMedGoogle Scholar
• Durinovic Bello I., Hummel M., Ziegler A. G. Cellular immune response to diverse islet cell antigens in IDDM. Diabetes 1996; 45: 795–800
   PubMedGoogle Scholar
• Eisenbarth G. S., Ziegler A. G. Type 1 diabetes mellitus. Molecular Endocrinology: Basic Concepts and Clinical Correlations, B. D. Weintraub. Raven Press, New York 1995; 269–82
   Google Scholar
• Itoh N., Hanafusa T., Miyazaki A., Miyagawa J., Yam-Agata K., Yamamoto K., 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. 1993; 92: 2313–22
   PubMed Web of Science ®Google Scholar
• Sibley R. K., Sutherland D. E., Goetz F., Michael A. F. Recurrent diabetes mellitus in the pancreas iso-and allograft. A light and electron microscopic and immunohislochemical analysis of four cases. Lab. Invest. 1985; 53: 132–44
   PubMed Web of Science ®Google Scholar
• Like A. A., Biron C. A., Weringer E. J., Byman K., Sroczynski E., Guberski D. L. Prevention of diabetes in Bio-Breeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells. J. Exp. Med. 1986; 164: 1145–59
   PubMed Web of Science ®Google Scholar
• Kröncke K. D., Funda J., Berschick B., Kolb H., Kolb Bachofen V. Macrophage cytotoxicity towards isolated rat islet cells: neither lysis nor its protection by nicotinamide are beta-cell specific. Diabetologia 1991; 34: 232–8
   PubMedGoogle Scholar
• Rabinovitch A., Suarez-Pinzon W. L., Sorensen O. Interleukin 12 mRNA expression in islets correlates with /S-cell destruction in NOD mice. J. Autoimmun 1996; 9: 645–51
   PubMed Web of Science ®Google Scholar
• Bendelac A., Carnaud C, Boitard C., Bach J. F. Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells. J. Exp. Med. 1987; 166: 823–32
   PubMed Web of Science ®Google Scholar
• Wang B., Gonzalez A., Benoist C., Mathis D. The role of CD8+ T cells in the initiation of insulin-dependent diabetes mellitus. Eur. J. Immunol. 1996; 26: 1762–9
   PubMed Web of Science ®Google Scholar
• Katz J., Benoist C., Mathis D. Major histocompatibility complex class I molecules are required for the development of insulitis in non-obese diabetic mice. Eur. J. Immunol. 1993; 23: 3358–60
   PubMed Web of Science ®Google Scholar
• Todd J. A., Bell J. I., McDevitt H. O. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 1987; 329: 599–604
   PubMed Web of Science ®Google Scholar
• Chicz R. M., Urban R. G., Gorga J. C, Vignali D. A., Lane W. S., Strominger J. L. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J Exp. Med. 1993; 178: 27–47
   PubMed Web of Science ®Google Scholar
• Baum H., Davies H., Peakman M. Molecular mimicry in the MHC: hidden clues to autoimmunity?. Immunol. Today 1996; 17: 68–70
   Google Scholar
• Tisch R., McDevitt H. Insulin-dependent diabetes mellitus. Cell 1996; 85: 291–7
   PubMed Web of Science ®Google Scholar
• Cudworth A. G. Type I diabetes mellitus. Dia-betologiu 1978; 14: 281–91
   Google Scholar
• Durinovic-Bello I., Kadrnka-Lovrencic M., Frleta M., Balog V., Dumic M., Kalaftic Z., et al. HLA antigens in families of patients with insulin-dependent diabetes mellitus. Period. Biol 1979; 81: 205
   Google Scholar
• Todd J. A., Bell J. I., McDevitt H. O. HLA antigens and insulin-dependent diabetes. Nature 1988; 333: 710
   PubMed Web of Science ®Google Scholar
• TuomilehtoWolf E., Tuomilehto J., Cepaitis Z., Lounamaa R. New susceptibility haplotype for type 1 diabetes. DIME Study Group. Lancet 1989; 2: 299–302
   PubMedGoogle Scholar
• Kelly H., McCann V. J., Kay P. H., Dawkins R. L. Susceptibility to IDDM is marked by MHC supratypes rather than individual alleles. Immunogenetics 1985; 22: 643–51
   PubMed Web of Science ®Google Scholar
• Durinovic Bello I., Schendel D. J., Kastelan A., Segurado O. G. A novel diabetes-susceptibility HLA haplotype is present in the Croatian population. Tissue Antigens 1993; 41: 107–9
   PubMedGoogle Scholar
• Brown J. H., Jardetzky T. S., Gorga J. C, Stern L. J., Urban R. G., Strominger J. L., et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DRI [see comments]. Nature 1993; 364: 33–9
   PubMed Web of Science ®Google Scholar
• Stern L. J., Brown J. H., Jardetzky T. S., Gorga J. C, Urban R. G., Strominger J. L., et al. Crystal structure of the human class II MHC protein HLA-DRI complexed with an influenza virus peptide. Nature 1994; 368: 215–21
   PubMed Web of Science ®Google Scholar
• Jardetzky T. S., Gorga J. C, Busch R., Rothbard J., Strominger J. L., Wiley D. C. Peptide binding to HLA-DRI: a peptide with most residues substituted to alanine retains MHC binding. EMBO J 1990; 9: 1797–803
   PubMed Web of Science ®Google Scholar
• Rammensee H. G., Friede T., Stevanovic S. MHC ligands and peptide motifs: first listing. Immunogenetics 1995; 41: 178–228
   PubMed Web of Science ®Google Scholar
• Ronningen K. S., . HLA class II associations in insulin-dependent diabetes mellitus among Blacks, Cau-casoids and Japanese. HLA 1991, K. Tsuji, M. Aitawa, T. Sasazuki, et al. Oxford Science Publications, OxfordUK 1993; Vol. 1: 713–22
   Google Scholar
• Khalil I., . A restricted number of HLA-DQα/β heterodimers confer varying degrees of susceptibility to insulin-dependent diabetes mellitus. HLA 1991, K. Tsuji, M. Aitawa, T. Sasazuki, et al. Oxford Science Publications, OxfordUK 1993; Vol. 1: 483–492
   Google Scholar
• Hammer J., Gallazzi F., Bono E., Karr R. W., Guenot J., Valsasnini P., et al. Peptide binding specificity of HLA-DR4 molecules: correlation with rheumatoid arthritis association. J. Exp. Med. 1995; 181: 1847–55
   PubMed Web of Science ®Google Scholar
• Wucherpfennig K. W., Yu B., Bhol K., Monos D. S., Argyris E., Karr R. W., et al. Structural basis for major histocompatibility complex (MHC)-linked susceptibility to autoimmunity: charged residues of a single MHC binding pocket confer selective presentation of self-peptides in pemphigus vulgaris. Proc. Natl. Acad. Sci. U.S.A. 1995; 92: 11935–9
   PubMed Web of Science ®Google Scholar
• Reich E. P., von Grafenstein H., Barlow A., Swen-Son K. E., Williams K., Janeway C. A. J. Self peptides isolated from MHC glycoproteins of nonobese diabetic mice. J. Immunol 1994; 152: 2279–88
   PubMed Web of Science ®Google Scholar
• Bohme J., Schuhbaur B., Kanagawa O., Benoist C., Mathis D. MHC-linked protection from diabetes dissociated from clonal deletion of T cells. Science 1990; 249: 293–5
   PubMed Web of Science ®Google Scholar
• Thorsby E., Ronningen K. S. Particular HLA-DQ molecules play a dominant role in determining susceptibility or resistance to type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1993; 36: 371–7
   PubMedGoogle Scholar
• Kwok W. W., Domeier M. E., Raymond F. C, Byers P., Nepom G. T. Allele-specific motifs characterize HLA-DQ interactions with a diabetes-associated peptide derived from glutamic acid decarboxylase. J. Immunol 1996; 156: 2171–7
   PubMed Web of Science ®Google Scholar
• Tienari P. J., Tuomilehto-Wolf E., Peltonen L. DIME Study Group. HLA haplotypes in type 1 (insulin-dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus. Diabetologia 1992; 35: 254–60
   PubMed Web of Science ®Google Scholar
• Fennessy M., Metcalfe K., Hitman G. A., Niven M., Biro P. A., Tuomilehto J., et al. A gene in the HLA class I region contributes to susceptibility to IDDM in the Finnish population. Childhood Diabetes in Finland (DiMe) Study Group. Diabetologia 1994; 37: 937–44
   PubMed Web of Science ®Google Scholar
• Demaine A. G., Hibberd M. L., Mangles D., Mill-Ward B. A. A new marker in the HLA class I region is associated with the age at onset of IDDM. Diabetologia 1995; 38: 623–8
   PubMedGoogle Scholar
• Ikegami H., Kawaguchi Y., Ueda H., Fukuda M., Taka-Kawa K., Fujioka Y., et al. MHC-linked diabetogenic gene of the NOD mouse: molecular mapping of the 3' boundary of the diabetogenic region. Biochem. Biophys. Res. Commun. 1993; 192: 677–82
   PubMedGoogle Scholar
• Wicker L. S., Leiter E. H., Todd J. A., Renjilian R. J., Peterson E., Fischer P. A., et al. Beta 2-microglobulin-deficient NOD mice do not develop insulitis or diabetes. Diabetes 1994; 43: 500–4
   PubMed Web of Science ®Google Scholar
• Lehmann P. V., Forsthuber T., Miller A., Ser-Carz E. E. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature 1992; 358: 155–7
   PubMed Web of Science ®Google Scholar
• Böhmer K., Keilacker H., Kuglin B., Hubinger A., Bertrams J., Gries F. A., et al. Proinsulin autoantibodies are more closely associated with type 1 (insulin-dependent) diabetes mellitus than insulin autoantibodies. Diabetologia 1991; 34: 830–4
   PubMedGoogle Scholar
• Drell D. W., Notkins A. L. Multiple immunological abnormalities in patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1987; 30: 132–43
   PubMed Web of Science ®Google Scholar
• Castano L., Russo E., Zhou L., Lipes M. A., Eisen-Barth G. S. Identification and cloning of a granule autoantigen (carboxypeptidase-H) associated with type 1 diabetes. J. Clin. Endocrinol. Metab. 1991; 73: 1197–201
   PubMed Web of Science ®Google Scholar
• Baekkeskov S., Aanstoot H. J., Christgau S., Reetz A., Solimena M., Cascalho M., et al. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 1990; 347: 151–6
   PubMed Web of Science ®Google Scholar
• Pietropaolo M., Castano L., Babu S., Buelow R., Kuo Y. L., Martin S., et al. Islet cell autoantigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen. J. Clin. Invest. 1993; 92: 359–71
   PubMed Web of Science ®Google Scholar
• Lan M. S., Lu J., Goto Y., Notkins A. L. Molecular cloning and identification of a receptor-type protein tyrosine phosphatase, IA-2, from human insulinoma. DNA Cell Biol 1994; 13: 505–14
   PubMed Web of Science ®Google Scholar
• Notkins A. L., Lu J., Qing L., Vander Vegt F. P., Wasser-Fall C, Maclaren N. K., Lan M. S. IA-2 and IA-2β are major autoantigens in IDDM and the precursors of the 40 kDa and 37 kDa tryptic fragments. J. Autoimm. 1996; 9: 677–82
   PubMedGoogle Scholar
• Hawkes C. J., Wasmeier C., Christie M. R., Hut-Ton J. C. Identification of the 37-kDa antigen in IDDM as a tyrosine phosphatase-like protein (phogrin) related to IA-2. Diabetes 1996; 45: 1187–92
   PubMed Web of Science ®Google Scholar
• Aanstoot H. J., Kang S. M., Kim J., Lindsay L. A., Roll U., Knip M., et al. 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
   PubMed Web of Science ®Google Scholar
• Christie M. R., Hollands J. A., Brown T. J., Michelsen B. K., Delovitch T. L. Detection of pancreatic islet64,000 M(r) autoantigens in insulin-dependent diabetes distinct from glutamate decarboxylase. J. Clin. Invest 1993; 92: 240–8
   PubMed Web of Science ®Google Scholar
• Boitard C., Villa M. C, Becourt C., Gia H. P., Hue C., Sempe P., et al. Peripherin: an islet antigen that is cross-reactive with nonobese diabetic mouse class II gene products. Proc. Natl. Acad. Sci. U.S.A. 1992; 89: 172–6
   PubMedGoogle Scholar
• Arden S. D., Roep B. O., Neophytou P. I., Usac E. F., Duinkerken G., de Vries R. R., et al. 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
   PubMed Web of Science ®Google Scholar
• Honeyman M. C., Cram D. S., Harrison L. C. Transcription factor jun-B is target of autoreactive T-cells in IDDM. Diabetes 1993; 42: 626–30
   PubMed Web of Science ®Google Scholar
• Endl J., Otto H., Jung G., Dreisbusch B., Donie F., Stahl P., Elbracht R., Schmitz G., Meinl E., Zieglar A.-G., Wank R., Schendel D. J. Identification of T cell epitopes of glutamic acid decarboxylase presented in the context of HLA-DR alleles by T lymphocytes of recent onset IDDM patients. J Exp Med 1997; 99: 2405–15
   Google Scholar
• Lohmann T., Leslie R. D., Londei M. T cell clones to epitopes of glutamic acid decarboxylase 65 raised from normal subjects and patients with insulin-dependent diabetes. J. Autoimmun. 1996; 9: 385–9
   PubMedGoogle Scholar
• Genovese S., Bonfanti R., Bazzigaluppi E., Lampa-Sona V., Benazzi E., Bosi E., Chiumello G., Bonifacio E. Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM. Diabetologia 1996; 39: 1223–6
   PubMedGoogle Scholar
• Roep B. O., Duinkerken G., Schreuder G. M., Kolb H., de Vries R. R., Martin S. HLA-associated inverse correlation between T cell and antibody responsiveness to islet autoantigen in recent-onset insulin-dependent diabetes mellitus. Eur. J. Immunol. 1996; 26: 1285–9
   PubMed Web of Science ®Google Scholar
• Griffing W. L., Moore S. B., Luthra H. S., McKenna C. H., Fathman C. G. Associations of antibodies to native DNA with HLA-DRw3. A possible major histocompatibility complex-linked human immune response gene. J. Exp. Med. 1980; 152: 319–25
   Google Scholar
• Steiner D. F., Clark J. L., Nolan C., Rubenstein A. H., Margoliash E., Aten B., et al. Proinsulin and the biosynthesis of insulin. Recent. Prog. Norm. Res. 1969; 25: 207–82
   PubMedGoogle Scholar
• Larger E., Becourt C., Bach J. F., Boitard C. Pancreatic islet beta cells drive T cell-immune responses in the nonobese diabetic mouse model. J. Exp. Med. 1995; 181: 1635–42
   PubMedGoogle Scholar
• Keller R. J. Cellular immunity to human insulin in individuals at high risk for the development of type I diabetes mellitus. J. Autoimmun. 1990; 3: 321–7
   PubMed Web of Science ®Google Scholar
• Schloot N. C., Roep B. O., Wegmann D., Yu L., Chase H. P., Wang T., Eisenbarth G. S. Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects. Diabetologia 1997; 40: 564–672
   PubMed Web of Science ®Google Scholar
• Rudy G., Brusic V., Harrison L. C., Lew A. M. Sequence similarity between beta-cell autoantigens. Immunol. Today 1995; 16: 406–7
   PubMedGoogle Scholar
• Rudy G., Stone N., Harrison L. C, Colman P. G., McNair P., Brusic V., et al. Similar peptides from two beta cell autoantigens, proinsulin and glutamic acid decarboxylase, stimulate T cells of individuals at risk for insulin-dependent diabetes. Mol. Med. 1995; 1: 625–33
   PubMed Web of Science ®Google Scholar
• Roll U., Christie M. R., Fuchtenbusch M., Payton M. A., Hawkes C. J., Ziegler A. G. Perinatal autoimmunity in offspring of diabetic parents. The German Mul-ticenter BABY-DIAB study: detection of humoral immune responses to islet antigens in early childhood. Diabetes 1996; 45: 967–73
   PubMedGoogle Scholar
• Kaufman D. L., ClareSalzler M., Tian J., Forsthuber T., Ting G. S., Robinson P., et al. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature 1993; 366: 69–72
   PubMed Web of Science ®Google Scholar
• Wegman D. R., Norbury-Glaser M., Daniel D. Insulin-Specific T cells are a predominant component of islet infiltrates in pre-diabetic NOD mice. Eur. J. Immunol. 1994; 24: 1853–57
   PubMedGoogle Scholar
• Daniel D., Wegman D. R. Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23). Proc. Natl. Acad. Sci. 1996; 93: 956–69
   PubMed Web of Science ®Google Scholar
• Tompkins S. M., Moore J. C., Jensen P. E. An insulin peptide that binds an alternative site in class II major histocompatibility complex. J. Exp. Med. 1996; 183: 857–66
   PubMedGoogle Scholar
• Jensen P. E., Kraft A. O. T cells from nonre-sponder mice. MHC restricted and unrestricted recognition of insulin. J. Immunol. 1990; 145: 3985–91
   PubMedGoogle Scholar
• Krug U., Krug F., Cuatrecasas P. Emergence of insulin receptors on human lymphocytes during in vitro transformation et at. Proc. Natl. Acad. Sci. U.S.A. 1972; 69: 2604–8
   PubMedGoogle Scholar
• DiazEspada F., LopezAlarcon L. Mitogen-induced changes in glycolytic enzymes of mouse lymphocytes: influence of insulin on cell activation in vitro. Immunology 1982; 46: 705–12
   PubMedGoogle Scholar
• Heldermanl J. H., Strom T. B. Role of protein and RNA synthesis in the development of insulin binding sites on activated thymus-derived lymphocytes. J. Biol. Chem. 1979; 254: 7203–7
   PubMedGoogle Scholar
• Strom T. B., Bear R. A., Carpenter C. B. Insulin-induced augmentation of lymphocyte-mediated cytotoxicity. Science 1975; 187: 1206–8
   PubMed Web of Science ®Google Scholar
• Bhakri H. L., Jones H., Jones D. A., Pettingale K. W., Tee D. E. H. T cell subpopulation dynamics following insulin-induced hypoglycemia in normal subjects. Clin. Exp. Immunol. 1983; 53: 83–7
   PubMedGoogle Scholar
• Pugliese A., Bugawan T., Moromisato R., Awdeh Z. L., Alper C. A., Jackson R. A., et al. Two subsets of HLA-DQA1 alleles mark phenotypic variation in levels of insulin autoantibodies in first degree relatives at risk for insulin-dependent diabetes. J. Clin. Invest. 1994; 93: 2447–52
   PubMedGoogle Scholar
• Ziegler R., Alper C. A., Awdeh Z. L., Castano L., Brink S. J., Soeldner J. S., et al. Specific association of HLA-DR4 with increased prevalence and level of insulin autoantibodies in first-degree relatives of patients with type 1 diabetes. Diabetes 1991; 40: 709–14
   PubMedGoogle Scholar
• Ziegler A. G., Standi E., Albert E., Mehnert H. HLA-associated insulin autoantibody formation in newly diagnosed type I diabetic patients. Diabetes 1991; 40: 1146–9
   PubMedGoogle Scholar
• Tisch R., Yang X. D., Singer S. M., Liblau R. S., Fug-Ger L., McDevitt H. O. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 1993; 366: 72–5
   PubMed Web of Science ®Google Scholar
• Dylan D., Wegmann D. R. Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23). Proc. Natl. Acad. Sci. U.S.A. 1996; 93: 956–60
   PubMedGoogle Scholar
• Zhang Z. J., Davidson L., Eisenbarth G., Weiner H. L. Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin. Proc. Natl. Acad. Sci. U.S.A. 1991; 88: 10252–6
   PubMed Web of Science ®Google Scholar
• Tian J., Lehmann P. V., Kaufman D. L. T cell cross-reactivity between coxsackievirus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele. J Exp. Med. 1994; 180: 1979–84
   PubMed Web of Science ®Google Scholar
• Elliott J. F., Qin H.-Y., Bhatti S., Smith D. K., Singh R. K., Dillon T., et al. Immunization with the larger isoform of mouse glutamic acid decarboxylase (GAD67) prevents autoimmune diabetes in NOD mice. Diabetes 1994; 43: 1494–9
   PubMed Web of Science ®Google Scholar
• Atkinson M. A., Bowman M. A., Campbell L., Dar-Row B. L., Kaufman D. L., Maclaren N. K. Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. J. Clin. Invest. 1994; 94: 2125–9
   PubMed Web of Science ®Google Scholar
• Lohmann T., Leslie R. D., Hawa M., Geysen M., Rod-Da S., Londei M. Immunodominant epitopes of glutamic acid decarboxylase 65 and 67 in insulin-dependent diabetes mellitus [see comments]. Lancet 1994; 343: 1607–8
   PubMed Web of Science ®Google Scholar
• Jones D. B., Crosby I. Proliferative lymphocyte responses to virus antigens homologous to GAD65 in IDDM. Diabetologia 1996; 39: 1318–24
   PubMed Web of Science ®Google Scholar
• Bruserud O., Jervell J., Thorsby E. HLA-DR3 and-DR4 control T-lymphocyte responses to mumps and Coxsackie B4 virus: studies on patients with type 1 (insulin-dependent) diabetes and healthy subjects. Diabetohgia 1985; 28: 420–6
   PubMedGoogle Scholar
• Delamaire M., Timsit J., Caillat Zucman S., Maugen-Dre D., Roussely H., Semana G., et al. HLA-associated heterogeneity of the humoral response to islet antigens in insulin-dependent diabetes. J. Autoimmun. 1995; 8: 645–57
   PubMedGoogle Scholar
• Passini N., Larigan J. D., Genovese S., Appella E., Sinigaglia F., Rogge L. The 37/40-kilodalton autoantigen in insulin-dependent diabetes mellitus is the putative tyrosine phosphatase IA-2. Proc. Natl. Acad. Sci. U.S.A. 1995; 92: 9412–6
   PubMed Web of Science ®Google Scholar
• Payton M. A., Hawkes C. J., Christie M. R. Relationship of the37,000-and40,000-M(r) tryptic fragments of islet antigens in insulin-dependent diabetes to the protein tyrosine phosphatase-like molecule IA-2 (ICA512). J. Clin. Invest. 1995; 96: 1506–11
   PubMed Web of Science ®Google Scholar
• Morrison D. C., Ryan Y. L. Endotoxins and disease mechanisms. Ann Rev Med 1987; 38: 417–32
   PubMed Web of Science ®Google Scholar
• Gegner J. A., et al. Lipopolysaccharide (LPS) signal transduction and clearance. Dual roles for LPS binding protein and membrane CD 14. J Biol Chem 1995; 270: 5320–25
   PubMed Web of Science ®Google Scholar
• Christie M. R., Genovese S., Cassidy D., Bosi E., Brown T. J., Lai M., et al. Antibodies to islet 37 k antigen, but not to glutamate decarboxylase, discriminate rapid progression to IDDM in endocrine autoimmunity. Diabetes 1994; 43: 1254–9
   PubMed Web of Science ®Google Scholar
• Leslie R. D. G., Elliott R. B. Perspectives in diabetes: Early environmental events as a cause of IDDM. Evidence and implications. Diabetes 1994; 43: 843–50
   PubMed Web of Science ®Google Scholar
• Fujita T., Yui R., Kusumoto J., Serizawa J., Makino S., Tochino Y. Lymphocyte insulitis in NOD (non-obese diabetic) mice: an immunohistochemical and electron microscope investigation. Biochem Res 1982; 3: 429–30
   Google Scholar
• Castano L., Eisenbarth G. S. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu. Rev. Immunol. 1990; 8: 647–79
   PubMed Web of Science ®Google Scholar
• Scherbaum W. A., Seissler J. Cellular and humoral autoimmunity in insulin-dependent diabetes mellitus. Exp. Clin. Endocrinol. 1995; 103: 88–94
   Google Scholar
• Hummel M., Durinovic Bello I., Ziegler A. G. Relation between cellular and humoral immunity to islet cell antigens in type I diabetes. J. Autoimmun. 1996; 9: 427–30
   PubMedGoogle Scholar
• Harrison L. C, Honeyman M. C, De Aizpurua H. J., et al. Inverse relation between humoral and cellular immunity to glutamic acid decarboxylase in subjects at risk of insulin-dependent diabetes. Lancet 1993; 341: 1365–1369
   PubMed Web of Science ®Google Scholar
• Watts C., Lanzavecchia A. Suppressive effect of antibody on processing of T cell epitopes. J Exp Med 1993; 178: 1459–1463
   PubMedGoogle Scholar
• Simitsek P. D., Campbell D. G., Lanzavecchia A., Fair-Weather N., Watts C. Modulation of antigen processing by bound antibodies can boost or suppress class II major histocompatibility complex presentation of different T cell determinants. J Exp Med 1995; 181: 1957–1963
   PubMedGoogle Scholar
• Lanzavecchia A. How can cryptic epitope.s trigger autoimmunity?. J Exp Med 1995; 181: 1945–1948
   PubMed Web of Science ®Google Scholar
• Honeyman M C, Harrison L. C, Drummond B., Col-Man P. G., Tait B. Analysis of families at risk for insulin-dependent diabetes mellitus reveals that HLA antigens influence progression to clinical disease. Molecular Medicine 1995; 5: 576–582
   Google Scholar
• Pfeffer C., Stein J., Southwood S., Ketelaar H., Sette A., Boltomly K. Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo. J. Exp Med 1995; 181: 1569–1574
   PubMedGoogle Scholar
• Pfeffer C., Murray J., Bottomly K. Selective activation of Thl and Th2 like cells in vivo. Response to human collagen IV. Immunol Rev 1991; 123: 65–84
   PubMedGoogle Scholar
• Dong X., Hamilton K. J., Satoh M., Wang J., Reeves W. H. Initiation of autoimmunity to the p53 tumor suppressor protein by complexes of p53 and SV40 large T antigen. J Exp Med 1994; 179: 1243–1252
   PubMed Web of Science ®Google Scholar
• Davies J. L., Kawaguchi Y., Bennett S. T., Copeman J. B., Cordell H. J., Pritchard L. E., et al. A genome-wide search for human type I diabetes susceptibility genes. Nature 1994; 371: 130–6
   PubMed Web of Science ®Google Scholar
• Bennett S. T., Lucassen A. M., Gough S. C. L., Powell E. E., Undlien D. E., Pritchard L. E., et al. Susceptibility to human type I diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nature Genetics 1995; 9: 284–292
   PubMed Web of Science ®Google Scholar
• Suzuki T., Yamada Y., Fujimura T., . Diabetogenic effects of lymphocyte transfusion on the NOD or NOD nude mouse. Immune-deficient animals in biomedical research, J. Rygaard, N. Brunner, N. Graem, N. Spang-Thomsen, et al. Karger, Basel 1987; 112–6
   Google Scholar
• Oldstone M. B. Viruses as therapeutic agents. Treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence. J. Exp. Med. 1990; 171: 2077–89
   PubMedGoogle Scholar
• Qin H. Y., Sadelain M. W., Hitchon C., Lauzon J., Singh B. Complete Freunďs adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice. J. Immunol. 1993; 150: 2072–80
   PubMed Web of Science ®Google Scholar
• Bach J. F. Predictive medicine in autoimmune diseases: from the identification of genetic predisposition and environmental influence to precocious immunothera-pie. Clin Immunol Immunopathol 1994; 72: 156–161
   PubMedGoogle Scholar
• Szopa T. M., Titchener P. A., Portwood N. D., Taylor K. W. Diabetes mellitus due to viruses-some recent developments. Diabetologia 1993; 36: 687–695
   PubMed Web of Science ®Google Scholar
• Rabinowe S. L., George K. L., Laughlin R., Soeld-Ner J. S., Eisenbarth G. S. Congenital rubella: monoclonal antibody defined T-cell abnormalities in young children. Am J Med 1986; 81: 779–782
   PubMed Web of Science ®Google Scholar
• Menser M. A., Forrest J. M., Bransby R. D. Rubella infection and diabetes mellitus. Lancet 1978; 1: 57–60
   PubMed Web of Science ®Google Scholar
• Ward K. P., Galloway W. H., Aucherlonie I. A. Congenital cytomegalovirus and diabetes. Lancet 1979; I: 497–99
   Google Scholar
• Park C.-Y., McArthur R. G., Eun H.-M., Yoon J.-W. Cytomegalovirus infection with autoimmune type I diabetes. Lancet 1979; I: 1–14
   Google Scholar
• Wagenknecht L. E., Roseman J. M., Herman W. H. Oncreased incidence of insulin dependent diabetes mellitus following an epidemic of Coxsackie B5. Am J Epidemiol 1991; 133: 1024–1031
   PubMedGoogle Scholar
• Petersen K. G., Heilmeyer P., Kerp L. Synthesis of proinsulin and large glucagon immunoreactivity in isolated islets of Largenhans from EMC virus infected mice. Diabetologia 1975; 11: 21–25
   PubMedGoogle Scholar
• Portwood N. D., Taylor K. W. Coxsackie B4 virus-induced changes in mouse pancreatic /S-cell mRNAs. Biochem Soc Trans 1990; 18: 1264–67
   PubMedGoogle Scholar
• Parkkonen P., Hyoty H., Koskinen L., Leinikki P. Mumps virus infects beta cells in human fetal islet cell cultures upregulating the expression of HLA class I molecules. Diabetologia 1992; 35: 63–69
   PubMedGoogle Scholar
• Cavallo M. G., Baroni M. G., Toto A., et al. Viral infection induces cytokine release by islet beta cells. Immunology 1992; 75: 664–668
   PubMed Web of Science ®Google Scholar
• Lefkovith J., Schreiner G., Cormier J., Handler E. S., Driscol H. F., Greiner D., et al. Prevention of diabetes in the BB rat by essential fatty acid deficiency: Relationship between physiological and biochemical changes. J Exp Med 1990; 171: 729–743
   PubMedGoogle Scholar
• Elliot R. B., Reddy S. N., Bibby N. J., Kida K. Dietary prevention of diabetes in the non-obese diabetic mouse. Diabetologia 1988; 31: 62–64
   PubMedGoogle Scholar
• Karges W., Hammond-McKibben D., Cheung R., Vis-Conti M., Shibuya N., Kemp D., et al. Immunological aspects of nutritional diabetes pretension in NOD mice. A pilot study for the cow's milk-based IDDM prevention trial. Diabetes 1997; 46: 557–564
   PubMed Web of Science ®Google Scholar
• Zauderer M., Campbell H., Johnson D. R., Seman M. Helper functions of antigen-induced specific and autoreactive T cell colonies. J. Mol. Cell Immunol. 1984; 1: 65–77
   PubMedGoogle Scholar
• Tilkin A. F., Michon J., Juy D., Kayibanda M., Hen-In Y., Sterkers G., et al. Autoreactive T cell clones of MHC class II specificities are produced during responses against foreign antigens in man. J. Immunol. 1987; 138: 674–9
   PubMed Web of Science ®Google Scholar
• Strober W., James S. P. Imniunoregulatory function of human autoreactive T-cell lines and clones. Immunol. Rev. 1990; 116: 117–38
   PubMedGoogle Scholar
• Kotani H., Mitsuya H., Jarrett R. F., Yenokida G. G., James S. P., Strober W. An autoreactive T cell clone that can be activated to provide both helper and suppressor function. J. Immunol. 1986; 136: 1951–9
   PubMed Web of Science ®Google Scholar
• Bensussan A., Metier S. C, Schlossman S. F., Reinherz E. L. Delineation of an imniunoregulatory amplifier population recognizing autologous la molecules. Analysis with human T cell clones. J. Exp. Med. 1984; 159: 559–76
   PubMedGoogle Scholar
• Kakkanaiah V. H., Seth A., Nagarkatti M., Nagar-Katti P. S. Autoreactive T cell clones isolated from normal and autoimmune-susceptible mice exhibit lymphokine secrectory and functional properties of both Thl and Th2 cells. Clin. Immunol. Immunopathol. 1990; 57: 148
   PubMedGoogle Scholar
• Miller G., Nepom G. T., Reich M. B., Thomas J. W. Autoreactive T cells from a type I diabetic recognize multiple class II products. Hum. Immunol 1993; 36: 219–26
   PubMedGoogle Scholar
• Glimcher L., Shevach E. M. Production of autoreactive I region-restricted T cell hybridomas. J. Exp. Med. 1982; 156: 640
   PubMed Web of Science ®Google Scholar
• Glimcher L. H., Serog B., McKean D. J., Beck B. N. Evidence that autoreactive T hybridomas recognize multiple epitopes on the I-Ak molecule. J. Immunol 1985; 134: 1780
   PubMedGoogle Scholar
• Imperiale M. J., Faherty D. A., Sproviero J. F., Zauderer M. Functionally distinct helper T cells enriched under different culture conditions cooperate with different B cells. J. Immunol. 1982; 129: 1843–8
   PubMedGoogle Scholar
• Wang Y., Perkins D. L. Characterization of autoreactive T cells: relative importance of self-peptides versus MHC. J. Immunol 1991; 147: 804
   PubMedGoogle Scholar
• French M. B., Allison J., Cram D. S., Thomas H. E., Dempsey-Collier M., Silva A., et al. Transgenic expression of mouse proinsulin II prevents diabetes in nonobese diabetic mice. Diabetes 1997; 46: 34–39
   PubMedGoogle Scholar
• Kuglin B., Cries F. A., Kolb H. Evidence of IgG autoantibodies against human proinsulin in patients with IDDM before insulin treatment. Diabetes 1988; 37: 130–2
   PubMed Web of Science ®Google Scholar
• Kuglin B., Haider B., Bertrams J., Gruneklee D., Gries F. A., Kolb H. Proinsulin autoantibodies: association with type I diabetes but not with islet cell antibodies, insulin autoantibodies or HLA-DR type. J. Auloimmun. 1990; 3: 573–7
   PubMedGoogle Scholar
• Kennedy G. C, German M. S., Rutter W. J. The minisatelite in the diabetes susceptibility locus IDDM2 regulates insulin transcription. Nature Genetics 1995; 9: 293–298
   PubMedGoogle Scholar