8
Views
16
CrossRef citations to date
0
Altmetric
Original Article

Insulin Dependent Diabetes Mellitus Hypothesis of Autoimmunity

, , &
Pages 221-235 | Received 22 Feb 1990, Accepted 22 Jun 1990, Published online: 07 Jul 2009

References

  • National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other‐ categories of glucose intoler ance. Diabetes. 1979; 28: 1039–1057
  • Bach J F. Mechanisms of autoimmunity in insulin‐dependent diabetes mellitus. Clin Exp Immunol. 1988; 72: 1–8
  • Hitchcock C L, Riley W J, Maclaren N K. Autoimmunity in insulin‐dependent diabetes mellitus: its detection and prevention. Concepts Immunopathol. 1988; 5: 144–167
  • Cohen I R. Insulin‐dependent diabetes mellitus. Curr Opinion Immunol. 1989; 1: 727–732
  • Gepts W. Pathology and anatomy of the pancreas in juvenile diabetes mellitus. Diabetes. 1965; 14: 619–633
  • Bottazzo G F, Dean B M, McNally J M, MacKay E H, Swift P G F, Gamble D R. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med. 1985; 313: 353–360
  • 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 immunohistochemical analysis of four cases. Lab Invest. 1985; 53: 132–144
  • Pozzilli P, Zuccarini O, Iavicoli M, Andreani D, Sensi M, Spencer K M, et al. Monoclonal antibodies defined abnormalities of T‐lymphocytes in type 1 (Insulin‐dependent) diabetes. Diabetes. 1983; 32: 91–94
  • Lederman M M, Ellner J J, Rodman H M. Defective suppressor cell generation in juvenile onset diabetes. J lmmunol. 1981; 127: 2051–2055
  • Quiniou‐Debrie M C, Debray‐Sachs M, Dardenne M, Czernichow P, Assan R, Bach J F. Anti‐islet cellular and humoral immunity, T‐cell subsets, and thymic function in Type 1 diabetes. Diabetes. 1985; 34: 373–379
  • Jackson R A, Morris M A, Haynes B F, Eisenbarth G S. Increased circulating Ia antigen‐bearing T cells in type I diabetes mellitus. N. Engl J Med. 1982; 306: 785–788
  • Lang F, Maugendre D, Houssaint E, Charbonnel B, Sai P. Cytoadherence of lymphocytes from type I diabetic subjects to insulin‐secreting cells. Market of anti‐beta‐cell cellular immunity. Diabeies. 1987; 36: 1356–1364
  • Topliss D, How J, Lewis M, Row V, Volpe R. Evidence for cell‐mediated immunity and specific suppressor T lymphocyte dysfunction in Graves' disease and diabetes melliltus. J Clin Endocrinol Metab. 1983; 57: 700–705
  • Legendre C M, Schiffrin A, Weitzner G, Colle E, Guttmann R D. Two‐color flow cytometry analysis of activated T‐ lymphocyte subsets in type I diabetes mellitus. Diahetes. 1988; 37: 792–795
  • Nicoletti F, Meroni P L, Barcellini W, Steinsväg P O, Di Mauro M, Lunetta M, et al. Enhanced percentage of CD5+ B lymphocytes in newly diagnosed IDDM patients. Immunol Lett. 1990; 23: 211–216
  • Huang S ‐W, Maclaren N K. Insulin‐dependent diabetes: a disease of autoaggression. Science 1976; 192: 64–66
  • Boitard C, Debray Sachs M, Pouplard A, Assan R, Hamburger J. Lymphocytes from diabetics suppress insulin release in vitro. Diabetologia. 1981; 21: 41–46
  • Lohmann D, Krug J, Lampeter E F, Bierwolf B, Verlohren H J. Cell‐mediated immune reactions against B cells and defect of suppressor cell activity in type I (insulin‐dependent) diabetes mellitus. Diabetologia. 1986; 29: 421–425
  • Neel J V. Diabetes mellitus‐A geneticist's nightmare. The genetics of diabetes mellitus, W Creutzfeldt, J Köbberling, J V Neel. Springer‐Verlag, Berlin 1976; 1–11
  • Tillil H, Köbberling J. Age‐corrected empirical genetic risk estimates for tirst‐degree relatives of IDDM patients. Diabetes. 1987; 36: 93–99
  • Trucco M, Dorman J S. lmmunogenetics of insulin‐dependent diabetes mellitus in humans. CRC Critical Reviews in Immunology. 1989; 9: 201–245
  • Segall M. HLA and eenetics of IDDM. Holism vs. reductionism. Diabetes. 1988; 37: 1005–1008
  • Foulis A K, Farquharson M A, 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 I (insulin‐dependent) diabetes mellitus. Diabetologia. 1987; 30: 333–343
  • Nepom B S, Palmer J, Kim S J, Hansen J A, Holbeck S L, Nepom G T. Specific genomic markers for the HLA‐DQ subregion discriminate between DR4+ insulin‐dependent diabetes mellitus and DR4+ seropositive juvenile rheumatoid arthritis. J Exp Med. 1986; 164: 345–350
  • Todd J A, Bell J I, McDevitt H O. HLA‐DQβ gene contributes to susceptibility and resistance to insulin‐dependent diabetes mellitus. Nature 1987; 329: 599–604
  • Morel P A, Dorman J S, Todd J A, McDevitt H O, Trucco M. Aspartic acid at position 57 of the HLA‐DQ beta chain protects against type 1 diabetes: a family study ‘published erratum appears in. Proc. Natl. Acad. Sci. (USA). 1989; 86: 13171, Proc Natl Acad Sci (USA) 1988, 85, 8111–8115
  • Yamagata K, Nakajima H, Hanafusa T, Noguchi T, Miyazaki A, Miyagawa J, et al. Aspartic acid at position 57 of DQβ chain does not protect against Type 1 (insulin‐dependent) diabetes mellitus in Japanese subjects. Diabetologia. 1989; 32: 762–764
  • Awata T, Kuzuya T, Matsuda A, Iwamoto Y, Kanazawa Y, Okuyama M, et al. High frequency of aspartic acid at position 57 of HLA‐DQ β‐chain in Japanese IDDM patients and nondiabetic subjects. Diabetes. 1990; 39: 266–269
  • Khail I, D'Auriol L, Gobet M, Morin L, Lepage V, Deschamp I, et al. A combination of HLA‐DQβ Asp57–negative and HLA‐DQα Arg52 confers susceptibility to insulin‐dependent diabetes mellitus. J Clin Invest. 1990; 85: 1315–1319
  • Rossini A A, Mordes J P, Handler E S. Speculations on etiology of diabetes mellitus: tumbler hypothesis. Diahetes. 1988; 37: 257–261
  • Hanafusa T, Pujol‐Borrell R, Chiovato L, Russell R C, Doniach D, Bottazzo G F. Aberrant expression of HLA‐DR antigen on thyrocytes in Graves' disease: relevance for autoim munity. Lancet. 1983; 2: 1111–1115
  • Buscema M, Todd I, Deuss U, Hammond L, Mirakian R, Pujol‐Borrell R, et al. Influence of tumor necrosis factor‐alpha on the modulation by interferon‐gamma of HLA class II molecules in human thyroid cells and its effect on interferon‐ gamma binding. J Clin Endocrinol Metab. 1989; 69: 433–439
  • Pujol‐Borrell R, Todd I, Doshi M, Bottazzo G F, Sutton R, Gray D, et al. HLA class II induction in human islet cells by interferon‐gamma plus tumour necrosis Factor or lymphotoxin. Nature 1987; 326: 304–306
  • Walker R, Bone A J, Cooke A, Baird J D. Aberrant expression of class II MHC molecules on pancreatic B‐cells during de velopment of insulin‐dependent diabetes: cause or conse quence?. Frontiers in diabetes research: Lesson from animal diabetes II, E Shafir, A E Renold. John Libbey, London 1988; 185–189
  • Foulis A K, Farquharson M A. Aberrant expression of HLA‐ DR antigens by insulin‐containing β‐cells in recent‐onset type 1 diabetes mellitus. Diabetes. 1986; 35: 1215–1224
  • Bottazzo G F, Pujol‐Borrell R, Hanafusa T, Feldmann M. Role of aberrant HLA‐DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet. 1983; 2: 1115–1119
  • Pujol‐Borrell R, Todd I. Inappropriate HLA class II in autoimmunity: is it the primary event?. Balliére's Clin Immunol Allergy 1987; 1: 1–27
  • Bottazzo G F, Foulis A K, Bosi E, Todd I, Pujol‐Borrell R. Pancreatic β‐cell damage. In search of novel pathogenetic factors. Diab Cure. 1988; 11(Suppl. I)24–28
  • Davies T F, Martin A, Graves P. Human autoimmune thyroid disease: cellular and molecular aspects. Ballière's Clin Endocrinol Metab. 1988; 2: 911–939
  • Londei M, Lamb J R, Bottazzo G F, Feldmann M. Epithelial cells expressing aberrant MHC class 11 determinants can present antigen to cloned human T cells. Nature 1984; 312: 639–641
  • Londei M, Bottazzo G F, Feldmann M. Human T‐cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells. Science 1985; 228: 85–89
  • Bottazzo G F, Florin‐Christensen A F, Donaich D. Islet cell antibodies in diabetes niellitus with autoimmune polyendo‐ crine deficiencies. Lancet. 1974; 2: 1279–1282
  • MacCuish A C, Irvine W J, Baines E W, Duncan L J. Antibodies to pancreatic islet cells in insulin‐dependent diabetics with coexistent autoimmune disease. Lancet. 1974; 2: 1529–1531
  • Srikanta S, Ganda O P, Jackson R A, Gleason R E, Kaldany A, Garovoy M D, et al. Type I diabetes mellitus in monozygotic twins: Chronic progressive beta cell dysfunction. Ann Intern Med. 1983; 99: 320–326
  • Dobersen M J, Scharff J E, Ginsberg‐Fellner F, Notkins A L. Cytotoxic autoantibodies to beta cells in the serum of patients with insulin‐dependent diabetes mellitus. N Engl J Med. 1980; 303: 1493–1498
  • Baekkeskov S, Nielsen J H, Marner B, Bilde T, Ludvigsson J, Lernmark Å. Autoantibodies in newly diagnosed diabetic children immunoprecipitate human pancreatic islet cell proteins. Nature 1982; 298: 167–169
  • Scherbaum W A, Mogel H, Boehm B O, Hedderich U, Gluck M, Schernthaner G, et al. Autoantibodies to adrenal medullary and thyroid calcitonin cells in type I diabetes mellitus‐a prospective study. J Autoimmun. 1988; 1: 219–230
  • Brown F M, Kamalesh M, Adri M N S, Rabinowe S L. Anti‐adrenal medullary antibodies in IDDM subjects and subjects at high risk of developing IDDM. Diab Care. 1988; 11: 30–33
  • Ziegler A G, Ziegler R, Vardi P, Jackson R A, Soeldner J S, Eisenbarth G S. Life‐table analysis of progression to diabetes of anti‐insulin autoantibody‐positive relatives of individuals with type 1 diabetes. Diabetes. 1989; 38: 1320–1325
  • Nuovo J A, Baker J R, Jr, Wartofsky L, Lukes Y G, Burman K D. Autoantibodies to insulin are present in sera of patients with autoimmune thyroid disease. Diabetes. 1988; 37: 317–320
  • Uchigata Y, Prabhakar B S, Salata K F, Ginsberg‐Fellner F, Notkins A L. Human monoclonal multiple‐organ‐reactive autoantibodies distinguished by mouse monoclonal anti‐ idiotypic antibodies: expression of idiotopes in humans with and without autoimmune diseases. J Immunol. 1987; 138: 4218–4221
  • Mouradian M, Abourizk N. Diabetes mellitus and thyroid disease. Diab Care. 1983; 6: 512–520
  • De Baets M H. Autoimmune endocrine diseases. Year Immunol. 1989; 4: 264–275
  • Rabinowe S L, Eisenbarth G S. Polyglandular autoimmmunity. Adv Intern Mrd. 1986; 31: 293–307
  • Payami H, Joe S, Thomson G. Autoimmune thyroid disease in type I diabetic families. Genet Epidemiol. 1989; 6: 137–141
  • Bougneres P F, Carel J C, Castano L, Boitard C, Gardin J P, Landais P, et al. Factors associated with early remission of type 1 diabetes in children treated with cyclosporine. N Engl J Med. 1988; 318: 663–670
  • Harrison L C, Colman P G, Dean B, Baxter R, Martin F I R. Increase in remission rate in newly diagnosed type 1 diabetic subjects treated with azathioprine. Diabetes. 1985; 34: 1306–1308
  • Silverstein J, Maclaren N, Riley W, Spillar R, Radjenovic D, Johnson S. Immunosuppression with azathioprine and prednisone in recent‐onset insulin‐dependent diabetes mellitus. N Engl J Med. 1988; 319: 599–604
  • Sutherland D E, Sibley R, Xu X Z, Michael A, Srikanta A M, Taub F, et al. Twin‐to‐twin pancreas transplantation: reversal and reenactment of the pathogenesis of type I diabetes. Trans Assoc Am Physicians. 1984; 97: 80–87
  • Campbell I L, Harrison L C. Viruses and cytokines: Evidence for multiple roles in pancreatic beta cell destruction in type I insulin‐dependent diabetes mellitus. Journal of Cellular Biochemistry. 1989; 40: 57–66
  • Leslie R D G, Pyke D A. Identical twins in diabetes. Immunology of diabetes, W J Irvine. Tevoit Scientific Publications, Edinburgh 1980; 101–108
  • Maugh T H. Diabetes: epidemiology suggests a viral connection. Science 1975; 188: 347–351
  • Menser M A, Forrest J M, Bransby R D. Rubella infection and diabetes mellitus. Lancet. 1978; 1: 57–60
  • Yoon J ‐W, Austin M, Onodera T, Notkins A L. Virus‐ induced diabetes mellitus. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med. 1979; 300: 1173–1179
  • Mordes J P, Desemone J, Rossini A A. The BB rat. Diabetes/Metab Rev. 1987; 3: 725–750
  • Parfrey N A, Prud'homme G J, Colle E, Fuks A, Seemayer T A, Guttmann R d. Immunologic and genetic studies of diabetes in the BB rat. CRC Crit Rev Immunol. 1989; 9: 45–65
  • Lampeter E F, Signore A, Gale E A M, Pozzilli P. Lessons from the NOD mouse for the pathogenesis and immunotherapy of human Type 1 (insulin‐dependent) diabetes mellitus. Diubetologia. 1989; 32: 703–708
  • Chappel C I, Chappel W R. The discovery and development of the BB rat colony: An animal model of spontaneous diabetes mellitus. Metabolism. 1983; 32(Suppl. 1)8–10
  • Butler L, Guberski D L, Like A A. Genetics of diabetes production in the Worcester colony of the BB rat. Frontiers in diabetes research: Lessons from unimal diabetes II, E Shafrir, A E Renold. John Libbey, London 1988; 74–78
  • Sternthal E, Like A A, Sarantis K, Braverman L E. Lymphocytic thyroiditis and diabetes in the BB/W rat. Diabetes. 1981; 30: 1058–1061
  • Voorby H A M, Van der Gaag R D, Jeucken P H M, Bloot A M, Drexhage H A. The goitre of the BB/O rat: An animal‐model for studying the role of immunoglobulins stimulating growth of thyroid cells. Clin Exper Immunol. 1989; 76: 290–295
  • Poussier P, Nakhooda A F, Falk J F, Lee C, Marliss E B. Lymphopenia and abnormal lymphocyte subsets in the “BB” rat: Relationship to the diabetic syndrome. Endocrinology. 1982; 110: 1825–1827
  • Elder M E, Maclaren N K. Identification of profound peripheral T lymphocyte immunodeficiencies in the spon taneously diabetic BB rat. J Immunol. 1983; 130: 1723–1731
  • Guttmann R D, Colle E, Michel F, Seemayer T. Spontaneous diabetes mellitus in the rat. I. I. T lymphopenia and its associa tion with clinical disease and pancreatic lymphocytic infiltra tion. J Immunol. 1983; 130: 1732–1735
  • Jackson R, Rassi N, Crump T, Haynes B, Eisenbarth G S. The BB diabetic rat: profound T‐cell lymphocytopenia. Dinbetes. 1981; 30: 887–889
  • Woda B A, Padden C. BioBreeding/Worcester (BB/Wor) rats are deficient in the generation of functional cytotoxic T cells. J Immunol. 1987; 139: 1514–1517
  • Like A A, Guberski D L, Butler L. Diabetic BioBreeding/ Worcester (BB/Wor) rats need not be lymphopenic. J Immunol. 1986; 136: 3254–3258
  • Makino S, Kunimoto K, Munaoko Y, Mizushima Y, Katagiri K, Tochino Y. Breeding of a non‐obese diabetic strain of mice. Exp Anim. 1980; 29: 1–13
  • Leiter E H, Serreze D V, Prochazaka M. The genetics and epidemiology of diabetes in NOD mice. Imrnunol Today. 1990; 11: 147–149
  • Kolb H. Mouse models of insulin dependent diabetes: Low‐ dose streptozotocin induced‐diabetes and nonobese diabetic (NOD) mice. Diaberesl Merab Rev. 1987; 3: 751–778
  • Sarvetnick N, Liggitt D, Pitts S L, Hansen S E, Stewart T A. Insulin‐dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon‐ gamma. Cell. 1988; 52: 773–782
  • Böhme J, Haskins K, Stecha P, van Ewijk W, LeMeur M, Gerlinger P, et al. Transgenic mice with I‐A on islet cells are normoglycemic but immunologically tolerant. Science 1989; 244: 1179–1183
  • Lo D, Burkly L C, Widera G, Cowing C, Flavell R A, Palmiter R D, et al. Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells. Cell. 1988; 53: 159–168
  • Allison J, Campbell I L, Morahan G, Mandel T E, Harrison L C, Miller J F A P. Diabetes in transgenic mice resulting from over‐expression of class I histocompatibility molecules in pancreatic beta cells. Nature 1988; 333: 529–533
  • Weringer E J, Like A A. Identification of T cell subsets and class I and class II antigen expression in islet grafts and pancreatic islets of diabetic BioBreeding/Worcester rats. Am J Pathol. 1988; 132: 292–303
  • Hanenberg H, Kolb‐Bachofen V, Kantwerk Funke G, Kolb H. Macrophage infiltration precedes and is a prerequisite for lymphocytic insulitis in pancreatic islets of pre‐diabetic BB rats. Diobetologia. 1989; 32: 126–134
  • Signore A, Pozzilli P, Gale E A, Andreani D, Beverley P C. The natural history of lymphocyte subsets infiltrating the pancreas of NOD mice. Diahetolngia. 1989; 32: 282–289
  • Koevary S, Rossini A A, Stoller W, Chick W, Williams R M. Passive transfer of diabetes in the BB/W rat. Science 1983; 220: 727–728
  • Koevary S B, Williams D E, Williams R M, Chick W L. Passive transfer of diabetes from BB/W to Wistar‐Furth rats. J Clin Invest. 1985; 75: 1904–1907
  • Gottlieb P A, Rossini A A, Mordes J P. Approaches to prevention and treatment of IDDM in animal models. Diab Cure. 1988; 11(Suppl. 1)29–36
  • Like A A, Kislauskis E, Williams R M, Rossini A A. Neonatal thymectomy prevents spontaneous diabetes mellitus in the BB/W rat. Science 1982; 216: 644–646
  • Like A A, Biron C A, Weringer E J, Byman K, Sroczynski E, Guberski D L. Prevention of diabetes in BioBreeding/ Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells. J Exp Med. 1986; 164: 1145–1159
  • Oschilewski U, Kiesel U, Kolb H. Administration of silica prevents diabetes in BB‐rats. Diabetes. 1985; 34: 197–199
  • Lefkowith J, Schreiner G, Cormier J, Handler E S, Driscoll H K, Greiner D, et al. Prevention of diabetes in the BB tat by essential fatty acid deficiency. Relationship between phy siological and biochemical changes. J Exp Med. 1990; 171: 729–743
  • Kiesel U, Oschilewski M, Kantwerk G, Maruta M, Hanenberg H, Treichel U, et al. Essential role of macro‐ phages in the development of Type I diabetes in BB rats. Transplatit Proc. 1986; 18: 1525–1527
  • Walker R, Bone A J, Cooke A, Baird J D. Distinct macrophage subpopulations in pancreas of prediabetic BB/E rats. Possible role for macrophages in pathogenesis of IDDM. Diabetes. 1988; 37: 1301–1304
  • Lee K U, Kim M K, Amano K, Pak C Y, Jaworski M A, Mehta J G, et al. Preferential infiltration of macrophages during early stages of insulitis in diabetes‐prone BB rats. Diabetes. 1988; 37: 1053–1058
  • Voorbij H A M, Jeucken P H M, Kabel P J, de Haan M, Drexhage H A. Dendritic cells and scavenger macrophages in pancreatic islets of prediabetic BB rats. Diabetes. 1989; 38: 1623–1629
  • Prowse S J, Bellgrau D, Lafferty K J. Islet allografts are destroyed by disease occurrence in the spontaneously diabetic BB rat. Diabetes. 1986; 35: 110–114
  • Kurner T, Burkart V, Kolb H. Large increase of cytotoxic/ suppressor T‐lymphoblasts and eosinophils around manifes tation of diabetes in BB rats. Diabetes Res. 1986; 3: 349–353
  • Nakhooda A F, Like A A, Chappel C I, Murray F T, Marliss E B. The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diobetes. 1977; 26: 100–112
  • Gotfredsen C F, Buschard K, Frandsen E K. Reduction of diabetes incidence of BB Wistar rats by early prophylactic insulin treatment of diabetes‐prone animals. Diabetologia. 1985; 28: 933–935
  • Baekkeskov S, Dyrberg T, Lernmark Å. Autoantibodies to a 64‐kilodalton islet cell protein precede the onset of spontaneous diabetes in the BB rat. Science 1984; 224: 1348–1350
  • Atkinson M A, Maclaren N K. Autoantibodies in nonobese diabetic mice immunoprecipitate 64, 000‐Mr islet antigen. Diabetes. 1988; 37: 1587–1590
  • Dotta F, Colman P G, Lombardi D, Scharp D W, Andreani D, Pontieri G M, et al. Ganglioside expression in human pancreatic islets. Diabetes. 1989; 38: 1478–1483
  • Dean B M, McNally J M, Bonifacio E, Jennings A M, Dunger D B, Gale E A M, et al. Comparison of insulin autoantibodies in diabetes‐related and healthy populations by precise displacement ELISA. Diabetes. 1989; 38: 1275–1281
  • Kämpe O, Anderson A, Björk E, Hallberg A, Karlsson F A. High‐glucose stimulation of 64, 000‐M, islet cell autoantigen expression. Diabetes. 1989; 38: 1326–1328
  • Weringer E J, Like A A. Immune attack on pancreatic islet transplants in the spontaneously diabetic BioBreeding/Worcester (BB/W) rat is not MHC restricted. J Immunol. 1985; 134: 2383–2386
  • Rossini A A, Williams R M, Mordes J P, Appel M C, Like A A. Spontaneous diabetes in the gnotobiotic BB/W rat. Diabetes. 1979; 28: 1031–1032
  • Prochazka M, Leiter E H, Serreze D V, Coleman D L. Three recessive loci required for insulin‐dependent diabetes in nonobese diabetic mice. Science Nov 11, 1988; 242(4880)9451, ‘published erratum appears in Science 1987, 237, 286–289
  • Wicker L S, Miller B J. MHC‐linked diabetogenic gene in the NOD mouse is not absolutely recessive. Annals of the New York Academy of Sciences 1988; 546: 240–241
  • Hattori M, Buse J B, Jackson R A, Glimcher L, Dorf M E, Minami M, et al. The NOD mouse: Recessive diabetogenic gene in the major histocompatibilty complex. Science 1986; 231: 733–735
  • Nishimoto H, Kikutani H, Yamamura K, Kishimoto T. Prevention of autoimmune insulitis by expression of I‐E molecules in NOD mice. Nature 1987; 328: 432–434
  • Acha Orbea H, McDevitt H O. The first external domain of the nonobese diabetic mouse class II I‐A beta chain is unique. Proc Natl Acad Sei (USA). 1987; 84: 2435–2439
  • Boitard C, Bendelac A, Richard M F, Carnaud C, Bach J F. Prevention of diabetes in nonobese diabetic mice by anti‐I‐A monoclonal antibodies: transfer of protection by splenic T cells. Proc Natl Acad Sci (USA). 1988; 85: 9719–9723
  • Jackson R A, Buse J B, Rifai R, Pelletier D, Milford E L, Carpenter C B, et al. Two genes required for diabetes in BB rats. Evidence from cyclical intercrosses and backcrosses. J Exp Med. 1984; 159: 1629–1636
  • Brayman K L, Markmann J F, Barker C F, Maji A. Immuno‐ prediction of diabetes and evaluation of pancreatic islet transplantation during the prediabetic period. Surgery. 1988; 104: 445–452
  • Guberski D L, Butler K, Kastern W, Like A A. Genetic studies in inbred BB/Wor rats: Analysis of progeny produced by crossing lymphopenic diabetes‐prone rats with nonlym‐phopenic diabetic rats. Diabetes. 1989; 38: 887–893
  • Woda B A, Like A A, Padden C, McFadden M. Deficiency of phenotypic cytotoxic‐suppressor T lymphocytes in the BB/W rat. J Immunol. 1986; 136: 856–859
  • Bellgrau D, Lagarde A C. Cytotoxic T‐cell precursors with low‐level CD8 in the diabetes‐prone Biobreeding rat: impli cations for generation of autoimmune T‐cell repertoire. Proc Natl Acad Sci (USA). 1990; 87: 313–317
  • Greiner D L, Handler E S, Nakano K, Mordes J P, Rossini A A. Absence of the RT‐6 T cell subset in diabetes‐prone BB/W rats. J Immunol. 1986; 136: 148–151
  • MacKay P, Jacobson J, Rabinovitch A. Spontaneous diabetes mellitus in the BioBreeding/Worcester rat. Evidence in vitro for natural killer cell lysis of islet cells. J Clin Invest. 1986; 77: 916–924
  • Woda B A, Biron C A. Natural killer cell number and function in the spontaneously diabetic BB/W rat. J Immunol. 1986; 137: 1860–1866
  • Nakamura N, Woda B A, Tafuri A, Greiner D L, Reynolds C W, Ortaldo J, et al. Natural killer cells are intrinsically cytotoxic to pancreatic islets. in vitro. Diabetes. 1990; 39: 836–842
  • Lang F, Kastern W. The gene for the T lymphocyte alloan‐ tigen, RT6, is not linked to either diabetes or lymphopenia and is not defective in the BB rat. Eur J Immunol. 1989; 19: 1785–1789
  • Gill T J I I I, Kunz H W, Misra D N, Cortese Hassett A L. The major histocompatibility complex of the rat. Transplantation. 1987; 43: 733–785
  • Colle E, Guttmann R D, Seemayer T A. Spontaneous diabetes mellitus in the rat. I. Association with the major histocom patibility complex. J Exp Med. 1981; 154: 1237–1242
  • Colle E, Guttmann R D, Fuks A. Insulin‐dependent diabetes mellitus is associated with genes that map to the right of the class 1 RT1. A locus of the major histocompatibility complex of the rat. Diabetes. 1986; 35: 454–458
  • Boitard C, Michie S, Serrurier P, Butcher G W, Larkins A P, McDevitt H O. In vivo prevention of thyroid and pancreatic autoimmunity in the BB rat by antibody to class II major histocompatibility complex gene products. Proc Natl Acad Sci (USA). 1985; 82: 6627–6631
  • Ono S J, Colle E, Guttmann R D, Fuks A. MHC association of IDDM maps to permissive immune response genes. The immunology of autoimmune diabetes mellitus, M A Jaworski, G D Molnar, R V Rajotte, B Singh. Elsevier, Amsterdam 1986; 51–57
  • Colle E, Guttmann R D, Seemayer T A, Michel F. Spontaneous diabetes mellitus syndrome in the rat. I. V. Immunogenetic interactions of MHC and non‐MHC components of the syndrome. Metabolism. 1983; 32(Suppl. 1)54–61
  • Chao N J, Timmerman L, McDevitt H O, Jacob C O. Molecular characterization of MHC class 11 antigens (beta 1 domain) in the BB diabetes‐prone and ‐resistant rat. Immunogenetics. 1989; 29: 231–234
  • Pollard D R, Gupta K, Mancino L, Hynie I. An immunofluorescence study of antipancreatic islet cell antibodies in the spontaneously diabetic BB Wistar rat. Diabetologia. 1983; 25: 56–59
  • Dyrberg T, Nakhooda A F, Baekkeskov S, Lernmark Å, Poussier P, Marliss E B. Islet cell surface antibodies and lymphocyte antibodies in the spontaneously diabetic BB Wistar rat. Diabetes. 1982; 31: 278–281
  • Dyrberg T, Poussier P, Nakhooda A F, Marliss E B, Lernmark Å. Humordl immunity in the spontaneously diabetic BB rat. Metabolism. 1983; 32(Suppl. I)87–91
  • Martin D R, Logothetopoulos J. Complement‐fixing islet cell antibodies in the spontaneously diabetic BB rat. Diabetes. 1984; 33: 93–96
  • Dyrberg T, Poussier P, Nakhooda A F, Baekkeskov S, Marliss E B, Lernmark A. Islet cell surface and lymphocyte antibodies often precede the spontaneous diabetes in the BB rat. Diabetologia. 1984; 26: 159–165
  • Elder M, Maclaren N, Riley W, McConnell T. Gastric parietal cell and other autoantibodies in the BB rat. Diabetes. 1982; 31: 313–318
  • Like A A, Appel M C, Rossini A A. Autoantibodies in the BB/W rat. Diabetes. 1982; 31: 816–820
  • Allen E M, Appel M C, Braverman L E. The effect of iodide ingestion on the development of spontaneous lymphocytic thyroiditis in the diabetes‐prone BB/W rat. Endocrinology. 1986; 118: 1977–1981
  • Reinhardt W, Appel M C, Alex S, Yang Y N, Braverman L E. The inhibitory effect of large doses of methimazole on iodine induced lymphocytic thyroiditis and serum anti‐thyrog‐ lobulin antibody titers in BB/Wor rats. Journal of Endocrinological Investigation. 1989; 12: 559–563
  • Colle E, Guttmann R D, Seemayer T A. Association of spon taneous thyroiditis with the major histocompatibility complex of the rat. Endocrinology. 1985; 116: 1243–1247
  • Rajatanavin R, Appel M C, Alex S, Yang Y, Reinhardt W, Braverman L E. Variable incidence of spontaneous and iodine induced lymphocytic thyroiditis in different lines of the BB/Wor rat. Endocrine Society, 71st Annual Meeting. Seattle, WA 1989; 477, (Abstract)
  • Laupacis A, Stiller C R, Gardell C, Keown P, Dupré J, Wallace A C, et al. Cyclosporin prevents diabetes in BB Wistar rats. Lancet. 1983; 1: 10–12
  • Jaworski M A, Honore L, Jewell L D, Mehta J G, McGuire‐ Clark P, Schouls J J, et al. Cyclosporin prophylaxis induces long‐term prevention of diabetes, and inhibits lymphocytic infiltration in multiple target tissues in the high‐risk BB rat. Diabetes Res. 1986; 3: 1–6
  • Like A A, Dirodi V, Thomas S, Guberski D L, Rossini A A. Prevention of diabetes mellitus in the BB/W rat with cyclosporin‐A. Am J Path. 1984; 117: 92–97
  • Like A A, Anthony M, Guberski D L, Rossini A A. Spon taneous diabetes mellitus in the BB/W rat. Effects of gluco‐ corticoids, cyclosporin‐A, and antiserum to rat lymphocytes. Diabetes. 1983; 32: 326–330
  • Like A A, Rossini A A, Guberski D L, Appel M C, Williams R M. Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Science 1979; 206: 1421–1423
  • Rossini A A, Slavin S, Woda B A, Geisberg M, Like A A, Mordes J P. Total lymphoid irradition prevents diabetes mellitus in the Bio‐BreedinglWorcester (BB/W) rat. Diabetes. 1984; 33: 543–547
  • Haskins K, Portas M, Bradley B, Wegmann D, Lafferty K. T‐lymphocyte clone specific for pancreatic islet antigen. Diabetes. 1988; 37: 1444–1448
  • Reich E ‐P, Scaringe D, Yagi J, Sherwin R S, Janeway C A, Jr. Prevention of diabetes in NOD mice by injection of auto‐reactive T‐lymphocytes. Diabetes. 1989; 38: 1647–1651
  • Nerup J, Mandrup Poulsen T, Mslvig J, Helqvist S, Wogensen L, Egeberg J. Mechanisms of pancreatic β‐cell destruction in type I diabetes. Diab Care. 1988; 11(Suppl. I)16–23
  • Bendtzen K, Mandrup‐Poulsen T, Nerup J, Nielsen J H, Dinarello C A, Svenson M. Cytotoxicity of human p17 interleukin‐1 for pancreatic islets of Langerhans. Science 1986; 232: 1545–1547
  • Palmer J P, Helqvist S, Spinas G A, Mslvig J, Mandrup‐Poul sen R, Andersen H U, et al. Interaction of β‐cell activity and IL‐I concentration and exposure time in isolated rat islets of Langcrhans. Diabetes. 1989; 38: 1211–1216
  • Pukel C, Baquerizo H, Rabinovitch A. Destruction of rat islet cell monolayers by cytokines. Synergistic interactions of interferon‐gamma, tumor necrosis factor, lymphotoxin. and interleukin 1. Diabetes. 1988; 37: 133–136
  • Kitagawa Y, Tafuri A, Greiner D L, Reynolds C, Ortaldo J, Rossini A A. Cytolysin (perforin) and natural killer cell cytotoxic factor are cytotoxic to islet cells but not thyrocytes. Diabetes. 1990; 39(Suppl. 1)97A, (Abstract)
  • Mordes J P, Rossini A A. Keys to understanding autoimmune diabetes mellitus: The animal models of insulin‐dependent diabetes mellitus. Ballière's Clin Immunol Allergy 1987; 1: 29–52
  • Karam J H, Lewitt P A, Young C W, Nowlain R E, Frankel B J, Fujiya H, et al. Insulinopenic diabetes after rodenticide (Vacor) ingestion: A unique model of acquired diabetes in man. Diabetes. 1980; 29: 971–978
  • Nomikos I N, Prowse S J, Carotenuto P, Lafferty K J. Combined treatment with nicotinamide and desferrioxamine prevents islet allograft destruction in NOD mice. Diabetes. 1986; 35: 1302–1304
  • Logothetopoulos J, Valiquette N, Madura E, Cvet D. The onset and progression of pancreatic insulitis in the overt, spontaneously diabetic, young adult BB rat studied by pancreatic biopsy. Diabetes. 1984; 33: 33–36
  • Seemayer T A, Colle E, Tannenbaum G S, Oligny L L, Guttmann R D, Goldman H. Spontaneous diabetes mellitus syndrome in the rat. III. Pancreatic alterations in aglycosuric and untreated diabetic BB Wistar‐derived rats. Metabolism. 1983; 32(Suppl. 1)26–32
  • Erb P, Grogg D, Troxler M, Kennedy M, Fluri M. CD4+ T cell‐mediated killing of MHC class II–positive antigen‐ presenting cells. I. characterization of target cell recognition by in vivo or in vitro activated CD4+ killer T cells. J. Immunol. 1990; 144: 790–795
  • Dean B M, Walker R, Bone A J, Baird J D, Cooke A. Pre‐ diabetes in the spontaneously diabetic BB/E rat: lymphocyte subpopulations in the pancreatic infiltrate and expression of rat MHC class II molecules in endocrine cells. Diabetologia. 1985; 28: 464–466
  • Voorby H A M, Kabel P J, de Haan M, Jeucken P H M, Van der Gaag R D, De Baets M H, et al. Dendritic cells and class II MHC expression on thyrocytes during the autoimmune thyroid disease of the BB rat. Clin Immunol Imrnunopathol. 1990; 55: 9–22
  • Int Veld P A, Pipeleers D G. In situ analysis of pancreatic islets in rats developing diabetes. Appearance of non‐ endocrine cells with surface MHC class II antigens and cyto‐ plasmic insulin immunoreactivity. J Clin Invest. 1988; 82: 1123–1128
  • Timsit J, Savino W, Boitard C, Bach J F. The role of class 11 major histocompatibility complex antigens in autoimmune diabetes: animal models. J Autoimmun. 1989; 2: 115–129
  • Markmann J F, Hickey W F, Kimura H, Woehrle M, Barker C F, Naji A. Gamma interferon induces novel expression of Ia antigens by rat pancreatic islet endocrine cells. Pancreas. 1987; 2: 258–261
  • Hanafusa T, Fujino Kurihara H, Miyazaki A, Yamada K, Nakajima H, Miyagawa J, et al. Expression of class II histo‐ compatibility complex antigens on pancreatic B cells in the NOD mouse. Diabetologia. 1987; 30: 104–108
  • Formby B, Miller N. Autologous CD4 T‐cell responses to ectopic class II major histocompatibility complex antigen‐ expressing single‐cell islet cells: an in vitro insight into the pathogenesis of lymphocytic insulitis in nonobese diabetic mice. Proc Natl Acad Sci (USA). 1990; 87: 2438–2442
  • Murphy K M, Weaver C T, Elish M, Allen P M, Loh D Y. Peripheral tolerance to allogeneic class II histocompatibility antigens expressed in transgenic mice: evidence against a clonal‐deletion mechanism. Proc Natl Acad Sci (USA). 1989; 86: 10034–10038
  • Harrison L C, Campbell I L, Allison J, Miller J F A P. MHC molecules and β‐cell destruction: Immune and nonimmune mechanisms. Diabetes. 1989; 38: 815–818
  • Markmann J, Lo D, Maji A, Palmiter R D, Brinster R L, Heber Katz E. Antigen presenting function of class II MHC expressing pancreatic beta cells. Nature 1988; 336: 476–479
  • Wicker L S, Miller B J, Mullen Y. Transfer of autoimmune diabetes mellitus with splenocytes from nonobese diabetic (NOD) mice. Diabetes. 1986; 35: 855–860
  • 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: 823–832
  • Hanafusa T, Sugihara S, Fujino Kurihara H, Miydgdwa J, Miyazaki A, Yoshioka T, et al. Induction of insulitis by adoptive transfer with L3T4 + Lyt2‐T‐lymphocytes in T‐ lymphocyte‐depleted NOD mice. Diabetes. 1988; 37: 204–208
  • Miller B J, Appel M C, O'Neil J J, Wicker L S. Both the Lyt‐ 2+ and L3T4+ Tcell subsets are required for the transfer of diabetes in nonobese diabetic mice. J Immunol. 1988; 140: 52–58
  • Bendelac A, Boitard C, Bedossa P, Bazin H, Bach J ‐F, Carnaud C. Adoptive T cell transfer of autoimmune nonobese diabetic mouse diabetes does not require recruit ment of host B lymphocytes. Journal of Immunology. 1988; 141: 2625–2628
  • LaFace D M, Peck A B. Reciprocal allogeneic bone marrow transplantation between NOD mice and diabetes‐nonsus‐ ceptible mice associated with transfer and prevention of autoimmune diabetes. Diabetes. 1989; 38: 894–901
  • Handler E S, Mordes J P, McKeever U, Nakamura N, Bernhard J, Greiner D I, et al. Effects of irradiation on diabetes in the BB/Wor rat. Autoimmunity. 1989; 4: 21–30
  • McKeever U, Mordes J P, Greiner D L, Appel M C, Rozing J, Handler E S, et al. Adoptive transfer of autoimmune diabetes and thyroiditis to athymic rats. Proc Natl Acad Sci (USA). 1990, (In press)
  • Hodes R J, Sharrow S O, Solomon A. Failure of T cell receptor Vβ negative selection in an athymic environment. Science 1989; 246: 1041–1044
  • Fry A, Jones L A, Kruisbeek A M, Matis L A. Thymic require ment for clonal deletion during T cell development. Science 1989; 246: 1044–1046
  • Speiser D E, Lees R K, Hengartner H, Zinkernagel R M, MacDonald H R. Positive and negative selection of T cell receptor Vβ domains controlled by distinct cell populations in the thymus. J Exp Med. 1989; 170: 2165–2170
  • Reich E ‐P, Sherwin R S, Kanagawa O, Janeway C A, Jr. An explanation for the protective effect of the MHC class II I‐E molecule in murine diabetes. Nature 1989; 341: 326–328
  • Kappler J W, Roehm N, Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987; 49: 273–280
  • Scott J, Engelhard V H, Benjamin D C. Bone marrow irradiation chimeras in the BB rat: Evidence suggesting two defects leading to diabetes and lymphopenia. Diabetologia. 1987; 30: 774–781
  • Rozing J, Coolen C, Tielen F J, Weegenaar J, Schuurman H ‐J, Greiner D L, et al. Defects in the thymic epithelial stroma of diabetes prone BB rats. Thymus. 1989; 140: 125–135
  • Georgiou H M, Lagarde A C, Bellgrau D. T cell dysfunction in the diabetes‐prone BB rat. A role for thymic migrants that are not T cell precursors. J Exp Med. 1988; 167: 132–148
  • Georgiou H M, Bellgrau D. Thymus transplantation and disease prevention in the diabetes‐prone Bio‐Breeding rat. J Immunol. 1989; 142: 3400–3405
  • Sakaguchi S, Fukuma K, Kuribyashi K, Masuda T. Organspecific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self‐tolerance: Deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med. 1985; 161: 72–87
  • Sakaguchi S, Sakaguchi N. Thymus and autoimmunity. Transplantation of the thymus from cyclosporin A‐treated mice causes organ‐specific autoimmune disease in athymic nude mice. J Exp Med. 1988; 167: 1479–1485
  • Yale J ‐F, Grose M, Marliss E B. Time course of the lymphopenia in BB rats. Relation to the onset of diabetes. Diabetes. 1985; 34: 955–959
  • Rossini A A, Mordes J P, Greiner D L, Nakano K, Appel M C, Handler E S. Spleen cell transfusion in the BB/W rat: Prevention of diabetes, MHC restriction, and long term per sistence of transfused cells. J Clin Invest. 1986; 77: 1399–1401
  • Burstein D, Mordes J P, Greiner D L, Stein D, Nakamura N, Handler E S, et al. Prevention of diabetes in the BB/Wor rat by a single transfusion of spleen cells: Parameters that affect the degree of protection. Diabetes. 1989; 38: 24–30
  • Greiner D L, Mordes J P, Handler E S, Angelillo M, Nakamura N, Rossini A A. Depletion of RT6.1+ T lympho cytes induces diabetes in resistant BioBreeding/Worcester (BB/W) rats. J Exp Med. 1987; 166: 461–475
  • Angelillo M, Greiner D L, Mordes J P, Handler E S, Nakamura N, McKeever U, et al. Absence of RT6+ T cells in diabetes‐prone BioBreeding/Worcester rats is due to genetic and cell developmental defects. J Immund. 1988; 141: 4146–4151
  • Thiele H ‐G, Koch F, Haag F, Wurst W. Evidence for normal thymic export of lymphocytes and an intact RT6a gene in RT6 deficient diabetes prone BB‐rats. Thymus. 1989; 14: 137–143
  • Crisá L, Greiner D L, Mordes J P, MacDonald R G, Handler E S, Czech M P, et al. Biochemical studies of RT6 alloantigens in BB/Wor and normal rats: Evidence for an intact but unexpressed RT6a structural gene in the diabetes prone BB rat. Diabetes. 1990, In press
  • Haag F, Koch F, Thiele H ‐G. Nucleotide and deduced amino acid sequence of the rat T‐cell alloantigen RT6.1. Nucleic Acids Res. 1990; 18: 1047–1047
  • Koch F, Haag F, Kashan A, Thiele H ‐G. Primary structure of rat RT6.2, a non‐glycosylated phosphatidylinositol‐linked surface marker of postthymic T cells. Proc Natl Acad Sci (USA). 1990; 87: 964–967
  • Klinkcrt W E, LaBadie J H, Bowers W E. Accessory and stimulating properties of dendritic cells and macrophages isolated from various rat tissues. J Exp Med. 1982; 156: 1–19
  • Voorbij J A M. Dendritic cells and the development of thyroid uutoimmune disease and Type I diabetes mellitus. Thesis Publishers, Amsterdam 1989
  • Harada M, Makino S. Suppression of overt diabetes in NOD mice by anti‐thymocyte serum or anti‐Thy 1.2 antibody. Exp Anim. 1986; 35: 501–504
  • Oschilewski M, Schwab E, Kiesel U, Opitz U, Stuenkel K, Kolb‐Bachofen V, et al. Administration of silica or monoclonal antibody to Thy‐I prevents low‐dose strepto‐ zotocin induced diabetes in mice. Immunol Lett. 1986; 12: 289–295
  • Gottlieb P A, Berrios J P, Mariani G, Handler E S, Greiner D, Mordes J P, et al. Autoimmune destruction of islets trans planted into RT6‐depleted diabetes‐resistant BB/Wor rats. Diabetes. 1990; 39: 643–645
  • Winter W E, Maclaren N K, Riley W J, Clarke D W, Kappy M S, Spillar R P. Maturity‐onset diabetes of youth in black americans. N Engl J Med. 1987; 316: 285–291
  • Mordes J P, McKeever U, Handler E S, Greiner D L, Burstein D, Rossini A A. “Immune modulation” of autoimmune diabetes in the BB rat. Frontiers in diabetes research: Lessons from animal diabetes II, A E Renold, E Shafrir. John Libbey & Co., London 1988; 167–173

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.