Insulin-Dependent Diabetes Mellitus as an Autoimmune Disease

Endocrine Reviews

Volumn 15, Issue 4, 1994, Pages 516-542

  Bach, Jean François ^a  

^a HÔPITAL NECKER ENFANTS MALADES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIGEN; CYTOKINE; HLA ANTIGEN; MAJOR HISTOCOMPATIBILITY ANTIGEN;

AUTOIMMUNITY; B LYMPHOCYTE; CLONAL ANERGY; ENVIRONMENTAL FACTOR; ETIOLOGY; GENETIC PREDISPOSITION; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOPATHOGENESIS; IMMUNOTHERAPY; INHERITANCE; INSULIN DEPENDENT DIABETES MELLITUS; MAJOR HISTOCOMPATIBILITY COMPLEX; MILK; MYCOBACTERIOSIS; NONHUMAN; PRIORITY JOURNAL; REVIEW; STRESS; T LYMPHOCYTE; THERAPY; VIRUS INFECTION;

ANIMAL; AUTOANTIGENS; AUTOIMMUNE DISEASES; DIABETES MELLITUS, EXPERIMENTAL; DIABETES MELLITUS, INSULIN-DEPENDENT; HUMAN; ISLETS OF LANGERHANS; SELF TOLERANCE;

EID: 0028026652     PISSN: 0163769X     EISSN: 0163769X     Source Type: Journal    
DOI: 10.1210/edrv-15-4-516     Document Type: Article

References (347)

1. Rossini AA, Greiner DL, Friedman HP, Mordes JP 1993 Immunopathogenesis of diabetes mellitus. Diabetes Rev 1:43-75
2. Honeyman MC, Harrison LC 1993 The immunologic insult in type 1 diabetes. Springer Semin Immunopathol 14:253-274
3. Castano L, Eisenbarth GS 1990 Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol 8:647-679
4. Bach JF 1988 Mechanisms of autoimmunity in insulin-dependent diabetes mellitus. Clin Exp Immunol 72:1-8
5. Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y 1980 Breeding of a non-obese, diabetic strain of mice. Exp Anim 29:1-13
6. Pozzilli P, Signore A, Williams AJ, Beales PE 1993 NOD mouse colonies around the world: recent facts and figures. Immunol Today 14:193-196
7. Bernard NF, Ertug F, Margolese H 1992 High incidence of thyroiditis and anti-thyroid autoantibodies in NOD mice. Diabetes 41:40-46
8. Baxter AG, Mandel TE 1991 Hemolytic anemia in non-obese diabetic mice. Eur J Immunol 21:2051-2055
9. Matsumoto M, Yagi H, Kunimoto K, Kawaguchi J, Makino S, Harada M 1993 Transfer of autoimmune diabetes from diabetic NOD mice to NOD athymic nude mice: the roles of T cell subsets in the pathogenesis. Cell Immunol 148:189-197
10. Christianson SW, Shultz LD, Leiter EH 1993 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-la donors. Diabetes 42:44-55
11. Harada M, Makino S 1984 Promotion of spontaneous diabetes in non-obese diabetes-prone mice by cyclophosphamide. Diabetologia 27:604-606
12. Yasunami R, Bach JF 1988 Anti-suppressor effect of cyclophosphamide on the development of spontaneous diabetes in NOD mice. Eur J Immunol 18:481-484
13. Nakhooda AF, Like A A, Chappel Cl, Murray FT, Marliss EB 1977 The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diabetes 26:100-112
14. Poussier P, Nakhooda AF, Falk JA, Lee C, Marliss EB 1982 Lymphopenia and abnormal lymphocyte subsets in the ‘BB’ rat: relationship to the diabetic syndrome. Endocrinology 110:1825-1827
15. Greiner DL, Handler ES, Nakano K, Mordes JP, Rossini A A 1986 Absence of the RT-6 T cell subset in diabetes-prone BB/W rats. J Immunol 136:148-151
16. Elias D, Markovits D, Reshef T, Van Der Zee R, Cohen IR 1990 Induction and therapy of autoimmune diabetes in the non-obese diabetic (NOD/Lt) mouse by a 65-kDa heat shock protein. Proc Natl Acad Sci USA 87:1576-1580
17. Elias D, Reshef T, Birk OS, Van Der Zee R, Walker MD, Cohen IR 1991 Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein. Proc Natl Acad Sci USA 88:3088-3091
18. Like AA, Rossini AA 1976 Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 193:415-417
19. Malaisse WJ 1982 Alloxan toxicity to the pancreatic B-cell. A new hypothesis. Biochem Pharmacol 31:3527-3534
20. Kolb H 1987 Mouse models of insulin dependent diabetes: lowdose streptozocin-induced diabetes and nonobese diabetic (NOD) mice. Diabetes Metab Rev 3:751-778
21. Paik SG, Fleischer N, Shin SI 1980 Insulin-dependent diabetes mellitus induced by subdiabetogenic doses of streptozotocin: obligatory role of cell-mediated autoimmune processes. Proc Natl Acad Sci USA 77:6129-6133
22. Gerling IC, Friedman H, Greiner DL, Shultz LD, Leiter EH 1994 Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes. Diabetes 43:433-440
23. Weide LG, Lacy PE 1991 Low-dose streptozotocin-induced autoimmune diabetes in islet transplantation model. Diabetes 40:1157-1162
24. Cockfield SM, Ramassar V, Urmson J, Halloran PF 1989 Multiple low dose streptozotocin induces systemic MHC expression in mice by triggering T cells to release IFN-gamma. J Immunol 142:1120-1128
25. Campbell IL, Oxbrow L, Koulmanda M, Harrison LC 1988 IFNgamma induces islet cell MHC antigens and enhances autoimmune, streptozotocin-induced diabetes in the mouse. J Immunol 140:1111-1116
26. Or low S, Yasunami R, Boitard C, Bach JF 1987 Induction précoce du diabéte chez la souris NOD par la streptozotocine. C R Acad Sd [III] 304:77-78
27. Ihm SH, Lee KU, McArthur RG, Yoon JW 1990 Predisposing effect of anti-beta cell autoimmune process in NOD mice on the induction of diabetes by environmental insults. Diabetologia 33:709-712
28. Taguchi O, Takahashi T, Nishizuka Y 1990 Self-tolerance and localized autoimmunity. Curr Opin Immunol 2:576-581
29. Fowell D, Mason D 1993 Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential. J Exp Med 177:627-636
30. Stumbles PA, Penhale WJ 1993 IDDM in rats induced by thymectomy and irradiation. Diabetes 42:571-578
31. McKeever U, Mordes JP, Greiner DL, Appel MC, Rozing J, Handler ES, Rossini AA 1990 Adoptive transfer of autoimmune diabetes and thyroiditis to athymic rats. Proc Natl Acad Sd USA 87:7618-7622
32. Adams TE, Alpert S, Hanahan D 1987 Non-tolerance and autoantibodies to a transgenic self antigen expressed in pancreatic beta cells. Nature 325:223-228
33. Sarvetnick N, Liggitt D, Pitts SL, Hansen SE, Stewart TA 1988 Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma. Cell 52:773-782
34. Sarvetnick N, Shizuru J, Liggitt D, Martin L, McIntyre B, Gregory A, Parslow T, Stewart T 1990 Loss of pancreatic islet tolerance induced by beta-cell expression of interferon-gamma. Nature 346:844-847
35. Stewart TA, Hultgren B, Huang X, Pitts-Meek S, Hully J, MacLachlan NJ 1993 Induction of type I diabetes by interferonalpha in transgenic mice. Science 260:1942-1946
36. Higuchi Y, Herrera P, Muniesa P, Huarte J, Belin D, Ohashi P, Aichele P, Orci L, Vassalli JD, Vassalli P 1992 Expression of a tumor necrosis factor alpha transgene in murine pancreatic beta cells results in severe and permanent insulitis without evolution towards diabetes. J Exp Med 176:1719-1731
37. Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA 1993 Transgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice. J Immunol 150:4136-4150
38. Wogensen L, Huang X, Sarvetnick N 1993 Leukocyte extravasation into the pancreatic tissue in transgenic mice expressing interleukin 10 in the islets of Langerhans. J Exp Med 178:175-185
39. Oldstone MB, Nerenberg M, Southern P, Price J, Lewicki H 1991 Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65:319-331
40. Roman LM, Simons LF, Hammer RE, Sambrook JF, Gething MJ 1990 The expression of influenza virus hemagglutinin in the pancreatic beta cells of transgenic mice results in autoimmune diabetes. Cell 61:383-396
41. Lo D, Freedman J, Hesse S, Palmiter RD, Brinster RL, Sherman LA 1992 Peripheral tolerance to an islet cell-specific hemagglutinin transgene affects both CD4+ and CD8+ T cells. Eur J Immunol 22:1013-1022
42. Scott B, Liblau R, Degermann S, Marconi LA, Ogata L, Caton AJ, McDevitt HO, Lo D 1994 A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity. Immunity 1:73-82
43. Ohashi PS, Oehen S, Buerki K, Pircher H, Ohashi CT, Odermatt B, Malissen B, Zinkernagel RM, Hengartner H 1991 Ablation of ‘tolerance’ and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65:305-317
44. Allison J, Campbell IL, Morahan G, Mandel TE, Harrison LC, Miller JF 1988 Diabetes in transgenic mice resulting from overexpression of class I histocompatibility molecules in pancreatic beta cells. Nature 333:529-533
45. Markmann J, Lo D, Naji A, Palmiter RD, Brinster RL, HeberKatz E 1988 Antigen presenting function of class II MHC expressing pancreatic beta cells. Nature 336:476-479
46. Gotz J, Eibel H, Kohler G 1990 Non-tolerance and differential susceptibility to diabetes in transgenic mice expressing major histocompatibility class II genes on pancreatic beta cells. Eur J Immunol 20:1677-1683
47. Bohme J, Haskins K, Stecha P, Van Ewijk W, Lemeur M, Gerlinger P, Benoist C, Mathis D 1989 Transgenic mice with I-A on islet cells are normoglycemic but immunologically intolerant. Science 244:1179-1183
48. Epstein PN, Overbeek PA, Means AR 1989 Calmodulin-induced early-onset diabetes in transgenic mice. Cell 58:1067-1073
49. Rotter JI, Vadheim CM, Rimoin DL 1990 Genetics of diabetes mellitus. In Rifkin H, Porte D (eds) Diabetes Mellitus. Theory and Practice, ed 4. Elsevier, Amsterdam, pp 378-413
50. Lo SS, Tun RY, Hawa M, Leslie RD 1991 Studies of diabetic twins. Diabetes Metab Rev 7:223-238
51. Singal DP, Blajchman MA 1973 Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus. Diabetes 22:429-432
52. Platz P, Jakobsen BK, Morling N, Ryder LP, Svejgaard A, Thomsen M, Christy M, Kromann H, Benn J, Nerup J, Green A, Hauge M 1981 HLA-D and -DR antigens in genetic analysis of insulin dependent diabetes mellitus. Diabetologia 21:108-115
53. Todd JA, Aitman TJ, Cornall RJ, Ghosh S, Hall JR, Hearne CM, Knight AM, Love JM, McAleer MA, Prins JB, Rodrigues N, Lathrop M, Pressey A, Delarato NH, Peterson LB, Wicker LS 1991 Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature 351:542-547
54. Wicker LS, Appel MC, Dotta F, Pressey A, Miller BJ, Delarato NH, Fischer PA, Boltz Jr RC, Peterson LB 1992 Autoimmune syndromes in major histocompatibility complex (MHC) congenic strains of nonobese diabetic (NOD) mice. The NOD MHC is dominant for insulitis and cyclophosphamide-induced diabetes. J Exp Med 176:67-77
55. Slattery RM, Kjer-Nielsen L, Allison J, Charlton B, Mandel TE, Miller JF 1990 Prevention of diabetes in non-obese diabetic I-Ak transgenic mice. Nature 345:724-726
56. Miyazaki T, Uno M, Uehira M, Kikutani H, Kishimoto T, Kimoto M, Nishimoto H, Miyazaki J, Yamamura K 1990 Direct evidence for the contribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mice. Nature 345:722-724
57. Lund T, O’reilly L, Hutchings P, Kanagawa O, Simpson E, Gravely R, Chandler P, Dyson J, Picard JK, Edwards A, Kioussis D, Cooke A 1990 Prevention of insulin-dependent diabetes mellitus in non-obese diabetic mice by transgenes encoding modified A beta-chain or normal I-E alpha-chain. Nature 345:727-729
58. Nishimoto H, Kikutani H, Yamamura K, Kishimoto T 1987 Prevention of autoimmune insulitis by expression of I-E molecules in NOD mice. Nature 328:432-434
59. Bohme J, Schuhbaur B, Kanagawa O, Benoist C, Mathis D 1990 MHC-linked protection from diabetes dissociated from clonal deletion of T cells. Science 249:293-295
60. Miyazaki T, Matsuda Y, Toyonaga T, Miyazaki J, Yazaki Y, Yamamura K 1992 Prevention of autoimmune insulitis in nonobese diabetic mice by expression of major histocompatibility complex class I Ld molecules. Proc Natl Acad Sri USA 89:9519-9523
61. Hattori M, Buse JB, Jackson RA, Glimcher L, Dorf ME, Minami M, Makino S, Moriwaki K, Kuzuya H, Imura H, Strauss WM, Seidman JG, Eisenbarth GS 1986 The NOD mouse: recessive diabetogenic gene in the major histocompatibility complex. Science 231:733-735
62. Acha-Orbea H, McDevitt HO 1987 The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique. Proc Natl Acad Sri USA 84:2435-2439
63. Podolin PL, Pressey A, Delarato NH, Fischer PA, Peterson LB, Wicker LS 1993 I-E+ nonobese diabetic mice develop insulitis and diabetes. J Exp Med 178:793-803
64. Colle E, Guttmann RD, Seemayer T 1981 Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex. J Exp Med 154:1237-1242
65. Colle E, Guttmann RD, Seemayer TA 1985 Association of spontaneous thyroiditis with the major histocompatibility complex of the rat. Endocrinology 116:1243-1247
66. Wassmuth R, Lernmark A 1989 The genetics of susceptibility to diabetes. Clin Immunol Immunopathol 53:358-399
67. Thorsby E, Ronningen KS 1993 Particular HLA-DQ molecules play a dominant role in determining susceptibility or resistance to type 1 (insulin-dependent) diabetes mellitus. Diabetologia 36:371-377
68. Baisch JM, Weeks T, Giles R, Hoover M, Stastny P, Capra JD 1990 Analysis of HLA-DQ genotypes and susceptibility in insulindependent diabetes mellitus. N Engl J Med 322:1836-1841
69. Caillat-Zucman S, Garchon HJ, Timsit J, Assan R, Boitard C, Djilali-Saiah I, Bougneres P, Bach JF 1992 Age-dependent HLA genetic heterogeneity of type 1 insulin-dependent diabetes mellitus. J Clin Invest 90:2242-2250
70. Todd JA, Bell JI, McDevitt HO 1987 HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329:599-604
71. Charron DJ, Lotteau V, Turmel P 1984 Hybrid HLA-DC antigens provide molecular evidence for gene trans-complementation. Nature 312:157-159
72. Ronningen KS, Undlien DE, Ploski R, Maouni N, Konrad RJ, Jensen E, Hornes E, Reijonen H, Colonna M, Monos DS, Strominger JL, Thorsby E 1993 Linkage disequilibrium between TAP2 variants and HLA class II alleles; no primary association between TAP2 variants and insulin-dependent diabetes mellitus. Eur J Immunol 23:1050-1056
73. Caillat-Zucman S, Bertin E, Timsit J, Boitard C, Assan R, Bach JF 1993 Protection from insulin-dependent diabetes mellitus is linked to a peptide transporter gene. Eur J Immunol 23:1784-1788
74. Bell GI, Horita S, Karam JH 1984 A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes 33:176-183
75. Julier C, Hyer RN, Davies J, Merlin F, Soularue P, Briant L, Cathelineau G, Deschamps I, Rotter JI, Froguel P, Boitard C, Bell JI, Lathrop GM 1991 Insulin-IGF2 region on chromosome 1 lp encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature 354:155-159
76. Bain SC, Prins JB, Hearne CM, Rodrigues NR, Rowe BR, Pritchard LE, Ritchie RJ, Hall JR, Undlien DE, Ronningen KS, Dunger DB, Barnett AH, Todd JA 1992 Insulin gene regionencoded susceptibility to type 1 diabetes is not restricted to HLADR4-positive individuals. Nat Genet 2:212-215
77. Lucassen AM, Julier C, Beressi JP, Boitard C, Froguel P, Lathrop M, Bell JI 1993 Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. Nat Genet 4:305-310
78. Avoustin P, Briant L, de Preval C, Cambon-Thomsen A 1992 Polymorphism study of TCR alpha and gamma genes in insulin dependent diabetes mellitus (IDDM) multiplex families. Autoimmunity 14:97-100
79. Martinez-Naves E, Coto E, Gutierrez V, Urra JM, Setien F, Dominguez O, Hood LE, Lopez-Larrea C 1991 Germline repertoire of T-cell receptor beta-chain genes in patients with insulindependent diabetes mellitus. Hum Immunol 31:77-80
80. Kelly H, Garlepp MJ 1993 T cell receptor haplotypes in families of patients with insulin-dependent diabetes mellitus. Clin Exp Immunol 91:226-231
81. Cornall RJ, Prins JB, Todd JA, Pressey A, Delarato NH, Wicker LS, Peterson LB 1991 Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/Ity/Bcg genes on chromosome 1. Nature 353:262-265
82. Garchon HJ, Bedossa P, Eloy L, Bach JF 1991 Identification and mapping to chromosome 1 of a susceptibility locus for periinsulitis in non-obese diabetic mice. Nature 353:260-262
83. Ghosh S, Palmer SM, Rodrigues NR, Cordell HJ, Hearne CM, Cornall RJ, Prins JB, McShane P, Lathrop GM, Peterson LB, Wicker LS, Todd JA 1993 Polygenic control of autoimmune diabetes in nonobese diabetic mice. Nat Genet 4:404-409
84. De Gouyon B, Melanitou E, Richard MF, Requarth M, Hahn IH, Guenet JL, Demenais F, Julier C, Lathrop GM, Boitard C, Avner P 1993 Genetic analysis of diabetes and insulitis in an interspecific cross of the nonobese diabetic mouse with Mus spretus. Proc Natl Acad Sci USA 90:1877-1881
85. Prins JB, Todd JA, Rodrigues NR, Ghosh S, Hogarth PM, Wicker LS, Gaffney E, Podolin PL, Fischer PA, Sirotina A, Peterson LB 1993 Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice. Science 260:695-698
86. Garchon HJ, Luan JJ, Eloy L, Bédossa P, Bach JF 1994 Genetic analysis of immune dysfunction in non-obese diabetic (NOD) mice: mapping of a susceptibility locus close to the Bcl-2 gene correlates with increased resistance of NOD T cells to apoptosis induction. Eur J Immunol 24:380-384
87. Jacob HJ, Pettersson A, Wilson D, Mao Y, Lernmark A, Lander ES 1992 Genetic dissection of autoimmune type I diabetes in the BB rat. Nat Genet 2:56-60
88. Diabetes Epidemiology Research International Group 1988 Geographic patterns of childhood insulin-dependent diabetes mellitus. Diabetes 37:1113-1119
89. Patrick SL, Moy CS, Laporte RE 1989 The world of insulindependent diabetes mellitus: what international epidemiologic studies reveal about the etiology and natural history of IDDM. Diabetes Metab Rev 5:571-578
90. Lefkowith J, Schreiner G, Cormier J, Handler ES, Driscoll HK, Greiner D, Mordes JP, Rossini AA 1990 Prevention of diabetes in the BB rat by essential fatty acid deficiency. Relationship between physiological and biochemical changes. J Exp Med 171: 729-743
91. Elliott RB, Reddy SN, Bibby NJ, Kida K 1988 Dietary prevention of diabetes in the non-obese diabetic mouse. Diabetologia 31: 62-64
92. Issa-Chergui B, Guttmann RD, Seemayer TA, Kelley VE, Colle E 1988 The effect of diet on the spontaneous insulin dependent diabetic syndrome in the rat. Diabetes Res 9:81-86
93. Oldstone MB 1990 Viruses as therapeutic agents. I. Treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence. J Exp Med 171:2077-2089
94. Oldstone MB, Ahmed R, Salvato M 1990 Viruses as therapeutic agents. II. Viral reassortants map prevention of insulin-dependent diabetes mellitus to the small RNA of lymphocytic choriomeningitis virus. J Exp Med 171:2091-2100
95. Takei I, Asaba Y, Kasatani T, Maruyama T, Watanabe K, Yanagawa T, Saruta T, Ishii T 1992 Suppression of development of diabetes in NOD mice by lactate dehydrogenase virus infection. J Autoimmun 5:665-673
96. Wilberz S, Partke HJ, Dagnaes-Hansen F, Herberg L 1991 Persistent MHV (mouse hepatitis virus) infection reduces the incidence of diabetes mellitus in non-obese diabetic mice. Diabetologia 34: 2-5
97. Like A A, Guberski DL, Butler L 1991 Influence of environmental viral agents on frequency and tempo of diabetes mellitus in BB/Wor rats. Diabetes 40:259-262
98. Bach JF 1994 Predictive medicine in autoimmune diseases: from the identification of genetic predisposition and environmental influence to precocious immunotherapy. Clin Immunol Immunopathol, in press
99. Guberski DL, Thomas VA, Shek WR, Like AA, Handler ES, Rossini AA, Wallace JE, Welsh RM 1991 Induction of type I diabetes by Kilham’s rat virus in diabetes-resistant BB/Wor rats. Science 254:1010-1013
100. Elliott RB, Martin JM 1984 Dietary protein: a trigger of insulindependent diabetes in the BB rat? Diabetologia 26:297-299
101. Daneman D, Fishman L, Clarson C, Martin JM 1987 Dietary triggers of insulin-dependent diabetes in the BB rat. Diabetes Res 5:93-97
102. Laakso M, Reunanen A, Klaukka T, Aromaa A, Maatela J, Pyorala K 1991 Changes in the prevalence and incidence of diabetes mellitus in Finnish adults, 1970-1987. Am J Epidemiol 133:850-857
103. Songini M, Muntoni S 1991 High incidence of type-I diabetes in Sardinia. Lancet 337:1047
104. Yoon JW, Ihm SH 1990 Viruses as a triggering factor of autoimmune type I diabetes. In Farid NR, Bona CA (eds) The Molecular Aspects of Autoimmunity. Academic Press, London, pp 231-240
105. Yoon JW 1991 Role of viruses in the pathogenesis of IDDM. Ann Med 23:437-445
106. MacDonald MJ, Liston L, Carlson I 1987 Seasonality in glycosylated hemoglobin in normal subjects. Does seasonal incidence in insulin-dependent diabetes suggest specific etiology? Diabetes 36:265-268
107. Menser MA, Forrest JM, Bransby RD 1978 Rubella infection and diabetes mellitus. Lancet 1:57-60
108. Yoon JW, Austin M, Onodera T, Notkins AL 1979 Virus induced diabetes mellitus. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 300:1173-1179
109. King ML, Shaikh A, Bidwell D, Voller A, Banatvala JE 1983 Coxsackie-B-virus-spedfic IgM responses in children with insulindependent (juvenile-onset; type I) diabetes mellitus. Lancet 1:1397-1399
110. Craighead JE, McLane MF 1968 Diabetes mellitus: induction in mice by encephalomyocarditis virus. Sdence 162:913-914
111. Haynes MK, Huber SA, Craighead JE 1987 Helper-inducer T-lymphocytes mediate diabetes in EMC-infected BALB/c ByJ mice. Diabetes 36:877-881
112. Buschard K, Rygaard J, Lung E 1976 The inability of a diabetogenic virus to induce diabetes mellitus in athymic (nude) mice. Acta Pathol Microbiol Scand C 84:299-303
113. Rayfield EJ, Kelly KJ, Yoon JW 1986 Rubella virus-induced diabetes in the hamster. Diabetes 35:1278-1281
114. Gaskins HR, Prochazka M, Hamaguchi K, Serreze DV, Leiter EH 1992 Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice. J Clin Invest 90:2220-2227
115. Suenaga K, Yoon JW 1988 Association of beta-cell-specific expression of endogenous retrovirus with development of insulitis and diabetes in NOD mouse. Diabetes 37:1722-1726
116. Thomas VA, Woda BA, Handler ES, Greiner DL, Mordes JP, Rossini A A 1991 Altered expression of diabetes in BB/Wor rats by exposure to viral pathogens. Diabetes 40:255-258
117. Kaufman DL, Erlander MG, Clare-Salzler M, Atkinson MA, MacLaren NK, Tobin AJ 1992 Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J Clin Invest 89:283-292
118. Sibley RK, Sutherland DE, Goetz F, Michael AF 1985 Recurrent diabetes mellitus in the pancreas isoand allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab Invest 53:132-144
119. Lampeter EF, Homberg M, Quabeck K, Schaefer UW, Wernet P, Bertrams J, Grosse-Wilde H, Gries FA, Kolb H 1993 Transfer of insulin-dependent diabetes between HLA-identical siblings by bone marrow transplantation. Lancet 341:1243-1244
120. Viallettes B, Maraninchi D 1993 Transfer of insulin-dependent diabetes between HLA-identical siblings by bone marrow transplantation. Lancet 342:174
121. Wang Y, Pontesilli O, Gill RG, La Rosa FG, Lafferty KJ 1991 The role of CD4+ and CD8+ T cells in the destruction of islet grafts by spontaneously diabetic mice. Proc Natl Acad Sd USA 88:527-531
122. Weringer EJ, Like AA 1985 Immune attack on pancreatic islet transplants in the spontaneously diabetic BioBreeding/Worcester (BB/W) rat is not MHC restricted. J Immunol 134:2383-2386
123. Sadelain MW, Qin HY, Lauzon J, Singh B 1990 Prevention of type I diabetes in NOD mice by adjuvant immunotherapy. Diabetes 39:583-589
124. Mclnerney MF, Pek SB, Thomas DW 1991 Prevention of insulitis and diabetes onset by treatment with complete Freund’s adjuvant in NOD mice. Diabetes 40:715-725
125. Sadelain MW, Qin HY, Sumoski W, Parfrey N, Singh B, Rabinovitch A 1990 Prevention of diabetes in the BB rat by early immunotherapy using Freund’s adjuvant. J Autoimmun 3: 671-680
126. Qin HY, Suarez WL, Parfrey N, Power RF, Rabinovitch A 1992 Mechanisms of complete Freund’s adjuvant protection against diabetes in BB rats: induction of non-specific suppressor cells. Autoimmunity 12:193-199
127. Yagi H, Matsumoto M, Kishimoto Y, Makino S, Harada M 1991 Possible mechanism of the preventive effect of BCG against diabetes mellitus in NOD mouse. II. Suppression of pathogenesis by macrophage transfer from BCG-vacdnated mice. Cell Immunol 138:142-149
128. Shehadeh N, Calcinaro F, Bradley BJ, Bruchlim I, Vardi P, Lafferty KJ 1994 Effect of adjuvant therapy on development of diabetes in mouse and man. Lancet 343:706-707
129. Renold AE 1985 Possible animal models for diabetes mellitus: syndromes involving toxic or immune etiology. In: Alberti KG, Krall LP (eds) The Diabetes Annual. Elsevier, Amsterdam, pp 492-508
130. Karam JH, Lewitt PA, Young CW, Nowlain RE, Frankel BJ, Fujiya H, Freedman ZR, Grodsky GM 1980 Insulinopenic diabetes after rodentidde (Vacor) ingestion: a unique model of acquired diabetes in man. Diabetes 29:971-978
131. Bouchard P, Sai P, Reach G, Caubarrere I, Ganeval D, Assan R 1982 Diabetes mellitus following pentamidine-induced hypoglycemia in humans. Diabetes 31:40-45
132. Karjalainen J, Martin JM, Knip M, Ilonen J, Robinson BH, Savilahti E, Akerblom HK, Dosch HM 1992 A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. N Engl J Med 327:302-307
133. Robinson BH, Dosch HM, Martin JM, Akerblom HK, Savilahti E, Knip M, Ilonen J 1993 A model for the involvement of MHC class II proteins in the development of type 1 (insulin-dependent) diabetes mellitus in response to bovine serum albumin peptides. Diabetologia 36:364-368
134. Dahlquist G, Savilahti E, Landin-Olsson M 1992 An increased level of antibodies to beta-lactoglobulin is a risk determinant for early-onset type 1 (insulin-dependent) diabetes mellitus independent of islet cell antibodies and early introduction of cow’s milk. Diabetologia 35:980-984
135. Karjalainen J, Saukkonen T, Savilahti E, Dosch HM 1992 Disease-assodated anti-bovine serum albumin antibodies in type 1 (insulin-dependent) diabetes mellitus are detected by particle concentration fluoroimmunoassay, and not by enzyme linked immunoassay. Diabetologia 35:985-990
136. Savilahti E, Saukkonen IT, Virtala ET, Tuomilehto J, Akerblom HK 1993 Increased levels of cow’s milk and beta-lactoglobulin antibodies in young children with newly diagnosed IDDM. Diabetes Care 16:984-989
137. Atkinson MA, Bowman MA, Kao KJ, Campbell L, Dush PJ, Shah SC, Simell O, MacLaren NK 1993 Lack of immune responsiveness to bovine serum albumin in insulin-dependent diabetes. N Engl J Med 329:1853-1858
138. Pietropaolo M, Castano L, Babu S, Buelow R, Kuo YL, Martin S, Martin A, Powers AC, Prochazka M, Naggert J, Leiter EH, Eisenbarth GS 1993 Islet cell autoantigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen. J Clin Invest 92:359-371
139. Surwit RS, Schneider MS, Feinglos MN 1992 Stress and diabetes mellitus. Diabetes Care 15:1413-1422
140. Ader DN, Johnson SB, Huang SW, Riley WJ 1991 Group size, cage shelf level, and emotionality in non-obese diabetic mice: impact on onset and inridence of IDDM. Psychosom Med 53: 313-321
141. Durant S, Coulaud J, Amrani A, El Hasnaoui A, Dardenne M, Homo-Delarche F 1993 Effects of various environmental stress paradigms and adrenalectomy on the expression of autoimmune type 1 diabetes in the nonobese diabetic (NOD) mouse. J Autoimmun 6:735-751
142. Williams AJ, Krug J, Lampeter EF, Mansfield K, Beales PE, Signore A, Gale EA, Pozzilli P 1990 Raised temperature reduces the inridence of diabetes in the NOD mouse. Diabetologia 33: 635-637
143. Fitzpatrick F, Lepault F, Homo-Delarche F, Bach JF, Dardenne M 1991 Influence of castration, alone or combined with thymectomy, on the development of diabetes in the nonobese diabetic mouse. Endocrinology 129:1382-1390
144. Fox HS 1992 Androgen treatment prevents diabetes in nonobese diabetic mice. J Exp Med 175:1409-1412
145. Rose NR, Bona C 1993 Defining criteria for autoimmune diseases (Witebsky’s postulates revisited). Immunol Today 14:426-430
146. Gaedigk R, Duncan AMV, Miyazaki I, Robinson BH, Dosch HM 1994 ICA1 encoding p69, a protein linked to the development of type 1 diabetes, maps to human chromosome 7p22. Cytogenet Cell Genet 66:274-276
147. Bendelac A, Carnaud C, Boitard C, Bach JF 1987 Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells. J Exp Med 166:823-832
148. Koevary S, Rossini A, Stoller W, Chick W, Williams RM 1983 Passive transfer of diabetes in the BB/W rat. Science 220:727-728
149. Haskins K, McDuffie M 1990 Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T cell clone. Science 249:1433-1436
150. Wicker LS, Miller BJ, Mullen Y 1986 Transfer of autoimmune diabetes mellitus with splenocytes from nonobese diabetic (NOD) mice. Diabetes 35:855-860
151. Shimizu J, Kanagawa O, Unanue ER 1993 Presentation of betacell antigens to CD4+ and CD8+ T cells of non-obese diabetic mice. J Immunol 151:1723-1730
152. Feutren G, Papoz L, Assan R, Vialettes B, Karsenty G, Vexiau P, Du Rostu H, Rodier M, Sirmai J, Lallemand A, Bach JF 1986 Cyclosporin increases the rate and length of remissions in insulindependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet 2:119-124
153. The Canadian-European Randomized Control Trial Group 1988 Cyclosporin-induced remission of IDDM after early intervention. Association of 1 yr of cyclosporin treatment with enhanced insulin secretion. Diabetes 37:1574-1582
154. Bach JF 1993 Strategies in immunotherapy of insulin-dependent diabetes mellitus. Ann NY Acad Sri, in press
155. Bottazzo GF, Florin-Christensen A, Doniach D 1974 Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 2:1279-1283
156. Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, de Camilli P 1990 Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347:151-156
157. Atkinson MA, Kaufman DL, Campbell L, Gibbs KA, Shah SC, Bu DF, Erlander MG, Tobin AJ, MacLaren NK 1992 Response of peripheral-blood mononuclear cells to glutamate decarboxylase in insulin-dependent diabetes. Lancet 339:458-459
158. Honeyman MC, Cram DS, Harrison LC 1993 Glutamic acid decarboxylase 67-reactive T cells: a marker of insulin-dependent diabetes. J Exp Med 177:535-540
159. Palmer JP, Asplin CM, Clemons P, Lyen K, Tatpati O, Raghu PK, Paquette TL 1983 Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 222:1337-1339
160. Kuglin B, Haider B, Bertrams J, Gruneklee D, Gries FA, Kolb H 1990 Proinsulin autoantibodies: association with type I diabetes but not with islet cell antibodies, insulin autoantibodies or HLADR type. J Autoimmun 3:573-577
161. Cabrera E, Fernandez LE, Carr A, Marquina G, Valiente O, Uriarte A, Rynmark BM, Fredman P, Svennerholm L 1992 Which glycolipids are the autoantigens of cytoplasmic islet cell antibodies ? Acta Diabetol 29:70-74
162. Genovese S, Bonifacio E, McNally JM, Dean BM, Wagner R, Bosi E, Gale EA, Bottazzo GF 1992 Distinct cytoplasmic islet cell antibodies with different risks for type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35:385-388
163. Dobersen MJ, Scharff JE, Ginsberg-Fellner F, Notkins AL 1980 Cytotoxic autoantibodies to beta cells in the serum of patients with insulin-dependent diabetes mellitus. N Engl J Med 303:1493-1498
164. Sai P, Boitard C, Debray-Sachs M, Pouplard A, Assan R, Hamburger J 1981 Complement-fixing islet cell antibodies from some diabetic patients alter insulin release in vitro. Diabetes 30: 1051-1057
165. Nerup J, Andersen OO, Bendixen G, Egeberg J, Poulsen JE 1971 Antipancreatic cellular hypersensitivity in diabetes mellitus. Diabetes 20:424-427
166. Harrison LC, de Aizpurua H, Loudovaris T, Campbell IL, Cebon JS, Tait BD, Colman PG 1991 Reactivity to human islets and fetal pig proislets by peripheral blood mononuclear cells from subjects with preclinical and clinical insulin-dependent diabetes. Diabetes 40:1128-1133
167. Harrison LC, Chu SX, de Aizpurua HJ, Graham M, Honeyman MC, Colman PG 1992 Islet-reactive T cells are a marker of preclinical insulin-dependent diabetes. J Clin Invest 89:1161-1165
168. Miller BJ, Appel MC, O’neil JJ, Wicker LS 1988 Both the Lyt-2+ and L3T4+ T cell subsets are required for the transfer of diabetes in nonobese diabetic mice. J Immunol 140:52-58
169. Edouard P, Hiserodt JC, Plamondon C, Poussier P 1993 CD8+ T-cells are required for adoptive transfer of the BB rat diabetic syndrome. Diabetes 42:390-397
170. Kloppel G, Altenahr E, Freytag G, Jansen FK 1974 Immune insulitis and manifest diabetes mellitus. Studies on the course of immune insulitis and the induction of diabetes mellitus in rabbits immunized with insulin. Virchows Arch [A] 364:333-346
171. Geenen V, Kroemer G 1993 Multiple ways to cellular immune tolerance. Immunol Today 14:573-575
172. Kaufman DL, Clare-Salzler M, Tian J, Forsthuber T, Ting GS, Robinson P, Atkinson MA, Sercarz EE, Tobin AJ, Lehmann PV 1993 Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature 366:69-72
173. Tisch R, Yang XD, Singer SM, Liblau RS, Fugger L, McDevitt HO 1993 Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 366:72-75
174. Gepts W, Lecompte PM 1981 The pancreatic islets in diabetes. Am J Med 70:105-115
175. Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR 1985 In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med 313:353-360
176. Hanninen A, Jalkanen S, Salmi M, Toikkanen S, Nikolakaros G, Simell O 1992 Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulindependent diabetes mellitus. J Clin Invest 90:1901-1910
177. Karlsson-Parra A, Kobbah M, Ewald U, Tuvemo T, Forsum U, Klareskog L 1988 Circulating class II transplantation antigenexpressing T lymphocytes in children with insulin-dependent diabetes mellitus at diagnosis. Acta Paediatr Scand 77:554-558
178. Chatenoud L, Feutren G, Nelson DL, Boitard C, Bach JF 1989 Effect of cyclosporin on interleukin 2-related T-lymphocyte parameters in IDDM patients. Diabetes 38:249-256
179. Giordano C, Galluzzo A, Marco A, Panto F, Amato MP, Caruso C, Bompiani GD 1988 Increased soluble interleukin-2 receptor levels in the sera of type 1 diabetic patients. Diabetes Res 8: 135-138
180. Munoz A, Gallart T, Vinas O, Gomis R 1991 Increased CD5positive B lymphocytes in type I diabetes. Clin Exp Immunol 83:304-308
181. MacKay P, Jacobson J, Rabinovitch A 1986 Spontaneous diabetes mellitus in the Bio-Breeding/Worcester rat. Evidence in vitro for natural killer cell lysis of islet cells. J Clin Invest 77:916-924
182. Rapoport MJ, Lazarus AH, Jaramillo A, Speck E, Delovitch TL 1993 Thymic T cell anergy in autoimmune nonobese diabetic mice is mediated by deficient T cell receptor regulation of the pathway of p21ras activation. J Exp Med 177:1221-1226
183. Sempe P, Ezine S, Marvel J, Bedossa P, Richard MF, Bach JF, Boitard C 1993 Role of CD4+CD45RA+ T cells in the development of autoimmune diabetes in the non-obese diabetic (NOD) mouse. Int Immunol 5:479-489
184. Savino W, Boitard C, Bach JF, Dardenne M 1991 Studies on the thymus in nonobese diabetic mouse. I. Changes in the microenvironmental compartments. Lab Invest 64:405-417
185. Savino W, Carnaud C, Luan JJ, Bach JF, Dardenne M 1993 Characterization of the extracellular matrix-containing giant perivascular spaces in the NOD mouse thymus. Diabetes 42:134-140
186. Nabarra B, Andrianarison I 1991 Thymus reticulum of autoimmune mice. 3. Ultrastructural study of NOD (non-obese diabetic) mouse thymus. Int J Exp Pathol 72:275-287
187. Rozing J, Coolen C, Tielen FJ, Weegenaar J, Schuurman HJ, Greiner DL, Rossini AA 1989 Defects in the thymic epithelial stroma of diabetes prone BB rats. Thymus 14:125-135
188. Rapoport MJ, Jaramillo A, Zipris D, Lazarus AH, Serreze DV, Leiter EH, Cyopick P, Danska JS, Delovitch TL 1993 Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice. J Exp Med 178:87-99
189. Boitard C, Larger E, Timsit J, Bach JF 1994 Insulin-dependent diabetes mellitus: an islet or an immune disease? Diabetologia, in press
190. Tron F, Bach JF 1989 Molecular and genetic characteristics of pathogenic autoantibodies. J Autoimmun 2:311-320
191. Pontes de Carvalho LC, Templeman J, Wick G, Roitt IM 1982 The role of self-antigen in the development of autoimmunity in Obese strain chickens with spontaneous autoallergic thyroiditis. J Exp Med 155:1255-1266
192. Berzofsky JA, Berkower IJ 1989 Immunogenicity and antigen structure. In: Paul WE (ed) Fundamental Immunology, ed 2. Raven Press, New York, vol 3:169-208
193. Baekkeskov S, Landin M, Kristensen JK, Srikanta S, Bruining GJ, Mandrup-Poulsen T, de Beaufort C, Soeldner JS, Eisenbarth G, Lindgren F, Sundquist G, Lernmark A 1987 Antibodies to a 64, 000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes. J Clin Invest 79:926-934
194. Bu DF, Erlander MG, Hitz BC, Tillakaratne NJ, Kaufman DL, Wagner-McPherson CB, Evans GA, Tobin AJ 1992 Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci USA 89: 2115-2119
195. Karlsen AE, Hagopian WA, Grubin CE, Dube S, Disteche CM, Adler DA, Barmeier H, Mathewes S, Grant FJ, Foster D, Lernmark A 1991 Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. Proc Natl Acad Sci USA 88:8337-8341
196. Hagopian WA, Karlsen AE, Gottsater A, Landin-Olsson M, Grubin CE, Sundkvist G, Petersen JS, Boel E, Dyrberg T, Lernmark A 1993 Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type. J Clin Invest 91: 368-374
197. Hagopian WA, Michelsen B, Karlsen AE, Larsen F, Moody A, Grubin CE, Rowe R, Petersen J, McEvoy R, Lernmark A 1993 Autoantibodies in IDDM primarily recognize the 65, 000-M(r) rather than the 67, 000-M(r) isoform of glutamic acid decarboxylase. Diabetes 42:631-636
198. Atkinson MA, Kaufman DL, Newman D, Tobin AJ, MacLaren NK 1993 Islet cell cytoplasmic autoantibody reactivity to glutamate decarboxylase in insulin-dependent diabetes. J CUn Invest 91: 350-356
199. Harrison LC, Honeyman MC, de Aizpurua HJ, Schmidli RS, Colman PG, Tait BD, Cram DS 1993 Inverse relation between humoral and cellular immunity to glutamic add decarboxylase in subjects at risk of insulin-dependent diabetes. Lancet 341: 1365-1369
200. Thivolet CH, Tappaz M, Durand A, Petersen J, Stefanutti A, Chatelain P, Vialettes B, Scherbaum W, Orgiazzi J 1992 Glutamic add decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals. Diabetologia 35:570-576
201. Christie MR, Tun RY, Lo SS, Cassidy D, Brown TJ, Hollands J, Shattock M, Bottazzo GF, Leslie RD 1992 Antibodies to GAD and tryptic fragments of islet 64K antigen as distinct markers for development of IDDM. Studies with identical twins. Diabetes 41:782-787
202. Christie MR, Vohra G, Champagne P, Daneman D, Delovitch TL 1990 Distinct antibody spedficities to a 64-kD islet cell antigen in type 1 diabetes as revealed by trypsin treatment. J Exp Med 172:789-794
203. Christie MR, Hollands JA, Brown TJ, Michelsen BK, Delovitch TL 1993 Detection of pancreatic islet 64, 000 M(r) autoantigens in insulin-dependent diabetes distinct from glutamate decarboxylase. J Clin Invest 92:240-248
204. Muir A, Luchetta R, Song HY, Peck A, Krischer J, MacLaren N 1993 Insulin immunization protects NOD mice from diabetes. Autoimmunity 15:58 (Abstract)
205. Zhang ZJ, Davidson L, Eisenbarth G, Weiner HL 1991 Suppression of diabetes in nonobese diabetic mice by oral administration of pordne insulin. Proc Natl Acad Sd USA 88:10252-10256
206. Atkinson MA, MacLaren NK, Luchetta R 1990 Insulitis and diabetes in NOD mice reduced by prophylactic insulin therapy. Diabetes 39:933-937
207. Thivolet CH, Goillot E, Bedossa P, Durand A, Bonnard M, Orgiazzi J 1991 Insulin prevents adoptive cell transfer of diabetes in the autoimmune non-obese diabetic mouse. Diabetologia 34:314-319
208. Gotfredsen CF, Buschard K, Frandsen EK 1985 Reduction of diabetes incidence of BB Wistar rats by early prophylactic insulin treatment of diabetes-prone animals. Diabetologia 28:933-935
209. Bertrand S, de Paepe M, Vigeant C, Yale JF 1992 Prevention of adoptive transfer in BB rats by prophylactic insulin treatment. Diabetes 41:1273-1277
210. Gottlieb PA, Handler ES, Appel MC, Greiner DL, Mordes JP, Rossini A A 1991 Insulin treatment prevents diabetes mellitus but not thyroiditis in RT6-depleted diabetes resistant BB/Wor rats. Diabetologia 34:296-300
211. Keller RJ, Eisenbarth GS, Jackson RA 1993 Insulin prophylaxis in individuals at high risk of type I diabetes. Lancet 341:927-928
212. Elias D, Cohen IR 1994 Peptide therapy for diabetes in NOD mice. Lancet 343:704-706
213. Roep BO, Arden SD, de Vries RR, Hutton JC 1990 T-cell clones from a type-1 diabetes patient respond to insulin secretory granule proteins. Nature 345:632-634
214. Roep BO, Kalian AA, Hazenbos WL, Bruining GJ, Bailyes EM, Arden SD, Hutton JC, de Vries RR 1991 T-cell reactivity to 38 kD insulin-secretory-granule protein in patients with recent-onset type 1 diabetes. Lancet 337:1439-1441
215. Boitard C, Villa MC, Becourt C, Gia HP, Hue C, Sempe P, Portier MM, Bach JF 1992 Peripherin: an islet antigen that is cross-reactive with nonobese diabetic mouse class II gene products. Proc Natl Acad Sci USA 89:172-176
216. Castano L, Russo E, Zhou L, Lipes MA, Eisenbarth GS 1991 Identification and cloning of a granule autoantigen (carboxypeptidase-H) assodated with type I diabetes. J Clin Endocrinol Metab 73:1197-1201
217. Nossal GJ, Herold KC, Goodnow CC 1992 Autoimmune tolerance and type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35 [Suppl 2]:S49-S59
218. Shehadeh NN, Gill RG, Lafferty KJ 1993 Mechanism of selftolerance to endocrine tissue. Springer Semin Immunopathol 14:203-220
219. Ametani A, Sercarz EE 1993 The nature of Band T-cell determinants. In: Bach JF (ed) Monoclonal Antibodies and Peptide Therapy in Autoimmune Diseases. Marcel Dekker, New York, vol: 13-28
220. Nakano N, Kikutani H, Nishimoto H, Kishimoto T 1991 T cell receptor V gene usage of islet beta cell-reactive T cells is not restricted in non-obese diabetic mice. J Exp Med 173:1091-1097
221. Katz JD, Wang B, Haskins K, Benoist C, Mathis D 1993 Following a diabetogenic T cell from genesis through pathogenesis. Cell 74:1089-1100
222. Acha-Orbea H 1993 T-cell receptors in autoimmune disease. In: Bach JF (ed) Monoclonal Antibodies and Peptide Therapy in Autoimmune Diseases. Marcel Dekker, New York, vol:131-142
223. O’reilly LA, Hutchings PR, Crocker PR, Simpson E, Lund T, Kioussis D, Takei F, Baird J, Cooke A 1991 Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression. Eur J Immunol 21:1171-1180
224. Toyoda H, Redford A, Magalong D, Chan E, Hosszufalusi N, Formby B, Teruya M, Charles MA 1992 In situ islet T cell receptor variable region gene usage in the nonobese diabetic mouse. Immunol Lett 32:241-245
225. Candeias S, Katz J, Benoist C, Mathis D, Haskins K 1991 Isletspecific T-cell clones from nonobese diabetic mice express heterogeneous T-cell receptors. Proc Natl Acad Sd USA 88:6167-6170
226. Bacelj A, Charlton B, Mandel TE 1989 Prevention of cyclophosphamide-induced diabetes by anti-V beta 8 T-lymphocyte-receptor monoclonal antibody therapy in NOD/Wehi mice. Diabetes 38:1492-1495
227. Taki T, Yokono K, Amano K, Hatamori N, Hirao Y, Tominaga Y, Maeda S, Kasuga M 1993 Effect of T-cell receptor V betaspedfic monoclonal antibodies on cyclophosphamide-induced diabetes mellitus in non-obese diabetic mice. Diabetologia 36: 391-396
228. Edouard P, Thivolet C, Bedossa P, Olivi M, Legrand B, Bendelac A, Bach JF, Carnaud C 1993 Evidence for a preferential V beta usage by the T cells which adoptively transfer diabetes in NOD mice. Eur J Immunol 23:727-733
229. Shizuru JA, Taylor-Edwards C, Livingstone A, Fathman CG 1991 Genetic dissection of T cell receptor V beta gene requirements for spontaneous murine diabetes. J Exp Med 174:633-638
230. Stein PH, Rees MA, Singer A 1992 Reconstitution of (BALB/c x B6)F1 normal mice with stem cells and thymus from nonobese diabetic mice results in autoimmune insulitis of the normal hosts’ pancreases. Transplantation 53:1347-1352
231. Nakano K, Mordes JP, Handler ES, Greiner DL, Rossini A A 1988 Role of host immune system in BB/Wor rat. Predisposition to diabetes resides in bone marrow. Diabetes 37:520-525
232. Leiter EH, Serreze DV 1991 Autoimmune diabetes in the nonobese diabetic mouse: suppression of immune defects by bone marrow transplantation and implications for therapy. Clin Immunol Immunopathol 59:323-334
233. Gold DP, Bellgrau D 1991 Identification of a limited T-cell receptor beta chain variable region repertoire assodated with diabetes in the BB rat. Proc Natl Acad Sd USA 88:9888-9891
234. Koevary SB, Blomberg M 1992 Prevention of diabetes in BB/Wor rats by intrathymic islet injection. J Clin Invest 89:512-516
235. Posselt AM, Barker CF, Friedman AL, Naji A 1992 Prevention of autoimmune diabetes in the BB rat by intrathymic islet transplantation at birth. Sdence 256:1321-1324
236. Kolb H, Zielasek J, Treichel U, Freytag G, Wrann M, Kiesel U 1986 Recombinant interleukin 2 enhances spontaneous insulindependent diabetes in BB rats. Eur J Immunol 16:209-212
237. Foulis AK, Farquharson MA, Hardman R 1987 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 (insulindependent) diabetes mellitus. Diabetologia 30:333-343
238. Kay TW, Campbell IL, Oxbrow L, Harrison LC 1991 Overexpression of class I major histocompatibility complex accompanies insulitis in the non-obese diabetic mouse and is prevented by antiinterferon-gamma antibody. Diabetologia 34:779-785
239. Ono SJ, Issa-Chergui B, Colle E, Guttmann RD, Seemayer TA, Fuks A 1988 IDDM in BB rats. Enhanced MHC class I heavychain gene expression in pancreatic islets. Diabetes 37:1411-1418
240. Hanafusa T, Fujino-Kurihara H, Miyazaki A, Yamada K, Nakajima H, Miyagawa J, Kono N, Tarui S 1987 Expression of class II major histocompatibility complex antigens on pancreatic B cells in the NOD mouse. Diabetologia 30:104-108
241. Signore A, Cooke A, Pozzilli P, Butcher G, Simpson E, Beverley PC 1987 Class-II and IL2 receptor positive cells in the pancreas of NOD mice. Diabetologia 30:902-905
242. Pujol-Borrell R, Todd I, Doshi M, Bottazzo GF, Sutton R, Gray D, Adolf GR, Feldmann M 1987 HLA class II induction in human islet cells by interferon-gamma plus tumour necrosis factor or lymphotoxin. Nature 326:304-306
243. Debray-Sachs M, Carnaud C, Boitard C, Cohen H, Gresser I, Bedossa P, Bach JF 1991 Prevention of diabetes in NOD mice treated with antibody to murine IFN gamma. J Autoimmun 4: 237-248
244. Campbell IL, Kay TW, Oxbrow L, Harrison LC 1991 Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest 87: 739-742
245. Nicoletti F, Meroni PL, Landolfo S, Gariglio M, Guzzardi S, Barcellini W, Lunetta M, Mughini L, Zanussi C 1990 Prevention of diabetes in BB/Wor rats treated with monoclonal antibodies to interferon-gamma. Lancet 336:319
246. Shehadeh NN, Larosa F, Lafferty KJ 1993 Altered cytokine activity in adjuvant inhibition of autoimmune diabetes, j Autoimmun 6:291-300
247. Thivolet C, Bendelac A, Bedossa P, Bach JF, Carnaud C 1991 CD8+ T cell homing to the pancreas in the nonobese diabetic mouse is CD4+ T cell-dependent. J Immunol 146:85-88
248. Laufer TM, Von Herrath MG, Grusby MJ, Oldstone MB, Glimcher LH 1993 Autoimmune diabetes can be induced in transgenic major histocompatibility complex class II-deficient mice. J Exp Med 178:589-596
249. Bach JF, Boitard C, Yasunami R, Dardenne M 1990 Control of diabetes in NOD mice by suppressor cells. J Autoimmun 3:97-100
250. Dardenne M, Lepault F, Bendelac A, Bach JF 1989 Acceleration of the onset of diabetes in NOD mice by thymectomy at weaning. Eur J Immunol 19:889-895
251. Sempé P, Richard MF, Bach JF, Boitard C 1994 Evidence of CD4+ regulatory T cells in the nonobese diabetic male mouse. Diabetologia 37:337-343
252. Boitard C, Yasunami R, Dardenne M, Bach JF 1989 T cellmediated inhibition of the transfer of autoimmune diabetes in NOD mice. J Exp Med 169:1669-1680
253. Pankewycz OG, Guan JX, Benedict JF 1992 A protective NOD islet-infiltrating CD8-IT cell clone, I.S. 2.15, has in vitro immunosuppressive properties. Eur J Immunol 22:2017-2023
254. Pankewycz O, Strom TB, Rubin-Kelley VE 1991 Islet-infiltrating T cell clones from non-obese diabetic mice that promote or prevent accelerated onset diabetes. Eur J Immunol 21:873-879
255. Diaz-Gallo C, Moscovitch-Lopatin M, Strom TB, Kelley VR1992 An anergic, islet-infiltrating T-cell clone that suppresses murine diabetes secretes a factor that blocks interleuldn 2/interleukin 4-dependent proliferation. Proc Natl Acad Sci USA 89:8656-8660
256. Boitard C, Bendelac A, Richard MF, Carnaud C, Bach JF 1988 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 85:9719-9723
257. Kawamura T, Nagata M, Utsugi T, Yoon JW 1993 Prevention of autoimmune type I diabetes by CD4+ suppressor T cells in superantigen-treated non-obese diabetic mice. J Immunol 151: 4362-4370
258. Formby B, Miller N, Peterson CM 1988 Adoptive immunotherapy of diabetes in autologous nonobese diabetic mice with lymphoid cells ex vivo exposed to cyclosporin plus interleukin 2. Diabetes 37:1305-1309
259. Greiner DL, Mordes JP, Handler ES, Angelillo M, Nakamura N, Rossini A A 1987 Depletion of RT6.1+ T lymphocytes induces diabetes in resistant biobreeding/Worcester (BB/W) rats. J Exp Med 166:461-475
260. Rossini AA, Faustman D, Woda BA, Like AA, Szymanski I, Mordes JP 1984 Lymphocyte transfusions prevent diabetes in the Bio-Breeding/Worcester rat. J Clin Invest 74:39-46
261. Mosmann TR, Coffman RL 1989 TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145-173
262. Slattery RM, Miller JFAP, Heath WR, Charlton B 1994 Failure of a protective major histocompatibility complex class II molecule to delete autoreactive T cells in autoimmune diabetes. Proc Natl Acad Sci USA 90:10808-10810
263. Singer SM, Tisch R, Yang XD, McDevitt HO 1993 An Abdtransgene prevents diabetes in nonobese diabetic mice by inducing regulatory T cells. Proc Natl Acad Sci USA 90:9566-9570
264. Hanafusa T, Miyazaki A, Miyagawa J, Tamura S, Inada M, Yamada K, Shinji Y, Katsura H, Yamagata K, Itoh N, Asakawa Nakagawa C, Otsuka A, Kawata S, Kono N, Tarui S 1990 Examination of islets in the pancreas biopsy specimens from newly diagnosed type 1 (insulin-dependent) diabetic patients. Diabetologia 33:105-111
265. Kay TW, Campbell IL, Harrison LC 1991 Characterization of pancreatic T lymphocytes associated with beta cell destruction in the non-obese diabetic (NOD) mouse. J Autoimmun 4:263-276
266. Yang XD, Karin N, Tisch R, Steinman L, McDevitt HO 1993 Inhibition of insulitis and prevention of diabetes in nonobese diabetic mice by blocking L-selectin and very late antigen 4 adhesion receptors. Proc Natl Acad Sci USA 90:10494-10498
267. Strandell E, Eizirik DL, Sandler S 1990 Reversal of beta-cell suppression in vitro in pancreatic islets isolated from nonobese diabetic mice during the phase preceding insulin-dependent diabetes mellitus. J Clin Invest 85:1944-1950
268. Sempe P, Bedossa P, Richard MF, Villa MC, Bach JF, Boitard C 1991 Anti-alpha/beta T cell receptor monoclonal antibody provides an efficient therapy for autoimmune diabetes in nonobese diabetic (NOD) mice. Eur J Immunol 21:1163-1169
269. Shah SC, Malone JI, Simpson NE 1989 A randomized trial of intensive insulin therapy in newly diagnosed insulin-dependent diabetes mellitus. N Engl J Med 320:550-554
270. Bendtzen K, Mandrup-Poulsen T, Nerup J, Nielsen JH, Dinarello CA, Svenson M 1986 Cytotoxicity of human pi 7 interleukin-1 for pancreatic islets of Langerhans. Science 232:1545-1547
271. Pukel C, Baquerizo H, Rabinovitch A 1988 Destruction of rat islet cell monolayers by cytokines. Synergistic interactions of interferon-gamma, tumor necrosis factor, lymphotoxin, and interleukin Diabetes 37:133-136
272. Pehuet-Figoni M, Ballot E, Bach JF, Chatenoud L 1992 The effects of interleukin-1 on pancreatic beta cell function in vitro depend on the glucose concentration. Eur Cytokine Netw 3: 443-450
273. Del Rey A, Besedovsky H 1989 Antidiabetic effects of interleukin 1. Proc Natl Acad Sci USA 86:5943-5947
274. Formby B, Jacobs C, Dubuc P, Shao T 1992 Exogenous administration of IL-1 alpha inhibits active and adoptive transfer autoimmune diabetes in NOD mice. Autoimmunity 12:21-27
275. Jacob CO, Aiso S, Michie SA, McDevitt HO, Acha-Orbea H 1990 Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1. Proc Natl Acad Sci USA 87:968-972
276. Satoh J, Seino H, Abo T, Tanaka S, Shintani S, Ohta S, Tamura K, Sawai T, Nobunaga T, Oteki T, Kumagai K, Toyota T 1989 Recombinant human tumor necrosis factor alpha suppresses autoimmune diabetes in nonobese diabetic mice. J Clin Invest 84:1345-1348
277. Corbett JA, Mikhael A, Shimizu J, Frederick K, Misko TP, McDaniel ML, Kanagawa O, Unanue ER 1993 Nitric oxide production in islets from nonobese diabetic mice: aminoguanidinesensitive and -resistant stages in the immunological diabetic process. Proc Natl Acad Sci USA 90:8992-8995
278. Bendelac A, Boitard C, Bedossa P, Bazin H, Bach JF, Carnaud C 1988 Adoptive T cell transfer of autoimmune nonobese diabetic mouse diabetes does not require recruitment of host B lymphocytes. J Immunol 141:2625-2628
279. Katz J, Benoist C, Mathis D 1993 Major histocompatibility complex class I molecules are required for the development of insulitis in non-obese diabetic mice. Eur J Immunol 23:3358-3360
280. Nagata M, Yokono K, Hayakawa M, Kawase Y, Hatamori N, Ogawa W, Yonezawa K, Shii K, Baba S 1989 Destruction of pancreatic islet cells by cytotoxic T lymphocytes in nonobese diabetic mice. J Immunol
281. 143:1155-1162
282. Young LH, Peterson LB, Wicker LS, Persechini PM, Young JD 1989 In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice. J Immunol 143:3994-3999
283. Boitard C, Chatenoud L, Debray-Sachs M 1982 In vitro inhibition of pancreatic B cell function by lymphocytes from diabetics with associated autoimmune diseases: a T cell phenomenon. J Immunol 129:2529-2531
284. Bradley BJ, Haskins K, La Rosa FG, Lafferty KJ 1992 CD8 T cells are not required for islet destruction induced by a CD4+ isletspecific T-cell clone. Diabetes 41:1603-1608
285. Maki T, Ichikawa T, Blanco R, Porter J 1992 Long-term abrogation of autoimmune diabetes in nonobese diabetic mice by immunotherapy with anti-lymphocyte serum. Proc Natl Acad Sci USA 89:3434-3438
286. Zavala AV, Fabiano de Bruno LE, Cardoso AI, Mota AH, Capucchio M, Poskus E, Fainboim L, Basabe JC 1992 Cellular and humoural autoimmunity markers in type 2 (non-insulin-dependent) diabetic patients with secondary drug failure. Diabetologia 35:1159-1164
287. Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, MacKay IR 1993 Antibodies to glutamic add decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulindependent onset of disease. Diabetes 42:359-362
288. Groop L, Groop PH, Koskimies S 1986 Relationship between B-cell function and HLA antigens in patients with type 2 (noninsulin-dependent) diabetes. Diabetologia 29:757-760
289. Irvine WJ, Sawers JS, Feek CM, Prescott RJ, Duncan LJ 1979 The value of islet cell antibody in predicting secondary failure of oral hypoglycaemic agent therapy in diabetes mellitus. J Clin Lab Immunol 2:23-26
290. Tuomilehto-Wolf E, Tuomilehto J, Hitman GA, Nissinen A, Stengard J, Pekkanen J, Kivinen P, Kaarsalo E, Karvonen MJ 1993 Genetic susceptibility to non-insulin dependent diabetes mellitus and glucose intolerance are located in HLA region. Br Med J 307:155-159
291. Thai AC, Eisenbarth GS 1993 Natural history of IDDM. Diabetes Rev 1:1-14
292. Palmer JP 1993 Predicting IDDM. Use of humoral immune markers. Diabetes Rev 1:104-115
293. Tarn AC, Thomas JM, Dean BM, Ingram D, Schwarz G, Bottazzo GF, Gale EA 1988 Predicting insulin-dependent diabetes. Lancet 1:845-850
294. Riley WJ, MacLaren NK, Krischer J, Spillar RP, Silverstein JH, Schatz DA, Schwartz S, Malone J, Shah S, Vadheim C, Rotter JI 1990 A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes. N Engl J Med 323:1167-1172
295. Barmeier H, McCulloch DK, Neifing JL, Warnock G, Rajotte RV, Palmer JP, Lernmark A 1991 Risk for developing type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies. Diabetologia 34:727-733
296. Gianani R, Pugliese A, Bonner-Weir S, Shiffrin AJ, Soeldner JS, Erlich H, Awdeh Z, Alper CA, Jackson RA, Eisenbarth GS 1992 Prognostically significant heterogeneity of cytoplasmic islet cell antibodies in relatives of patients with type I diabetes. Diabetes 41:347-353
297. Lewis CM, Canafax DM, Sprafka JM, Barbosa JJ 1992 Doubleblind randomized trial of nicotinamide on early-onset diabetes. Diabetes Care 15:121-123
298. Vague P, Picq R, Bernal M, Lassmann-Vague V, Vialettes B 1989 Effect of nicotinamide treatment on the residual insulin secretion in type 1 (insulin-dependent) diabetic patients. Diabetologia 32:316-321
299. Mendola G, Casamitjana R, Gomis R 1989 Effect of nicotinamide therapy upon B-cell function in newly diagnosed type 1 (insulindependent) diabetic patients. Diabetologia 32:160-162
300. Hutchings P, O’reilly L, Parish NM, Waldmann H, Cooke A 1992 The use of a non-depleting anti-CD4 monoclonal antibody to re-establish tolerance to beta cells in NOD mice. Eur J Immunol 22:1913-1918
301. Chatenoud L, Thervet E, Primo J, Bach JF 1993 Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci USA 91:123-127
302. Hurtenbach U, Lier E, Adorini L, Nagy ZA 1993 Prevention of autoimmune diabetes in non-obese diabetic mice by treatment with a class II major histocompatibility complex-blocking peptide. J Exp Med 177:1499-1504
303. Gerling IC, Serreze DV, Christianson SW, Leiter EH 1992 Intrathymic islet cell transplantation reduces beta-cell autoimmunity and prevents diabetes in NOD/Lt mice. Diabetes 41:1672-1676
304. Bougneres PF, Carel JC, Castano L, Boitard C, Gardin JP, Landais P, Hors J, Mihatsch MJ, Paillard M, Chaussain JL, Bach JF 1988 Factors associated with early remission of type I diabetes in children treated with cyclosporine. N Engl J Med 318:663-670
305. Silverstein J, MacLaren N, Riley W, Spillar R, Radjenovic D, Johnson S 1988 Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus. N Engl J Med 319:599-604
306. Cook JJ, Hudson I, Harrison LC, Dean B, Colman PG, Werther GA, Warne GL, Court JM 1989 Double-blind controlled trial of azathioprine in children with newly diagnosed type I diabetes. Diabetes 38:779-783
307. Bougneres PF, Landais P, Boisson C, Carel JC, Frament N, Boitard C, Chaussain JL, Bach JF 1990 Limited duration of remission of insulin dependency in children with recent overt type I diabetes treated with low-dose cyclosporin. Diabetes 39: 1264-1272
308. Burcelin RG, Eddouks M, Beylot M, Normand S, Boitard C, Feutren G, Landais P, Riou JP, Girard JR, Bach JF, Assan RI 1993 Hypersensitivity to insulin during remissions in cyclosporintreated IDDM patients. Diabetes Care 16:881-888
309. Hramiak IM, Dupre J, Finegood DT 1993 Determinants of clinical remission in recent-onset IDDM. Diabetes Care 16:125-132
310. Ogawa M, Maruyama T, Hasegawa T, Kanaya T, Kobayashi F, Tochino Y, Uda H 1985 The inhibitory effect of neonatal thymectomy on the incidence of insulitis in non-obese diabetic (NOD) mice. Biomed Res 6:103-105
311. Mori Y, Suko M, Okudaira H, Matsuba I, Tsuruoka A, Sasaki A, Yokoyama H, Tanase T, Shida T, Nishimura M, Terada E, Ikeda Y 1986 Preventive effects of cyclosporin on diabetes in NOD mice. Diabetologia 29:244-247
312. Miyagawa J, Yamamoto K, Hanafusa T, Itoh N, Nakagawa C, Otsuka A, Katsura H, Yamagata K, Miyazaki A, Kono N, Tarui S 1990 Preventive effect of a new immunosuppressant FK-506 on insulitis and diabetes in non-obese diabetic mice. Diabetologia 33:503-505
313. Strasser S, Cearns-Spielman J, Carroll P, Alejandro R1992 Effect of FK 506 on cyclophosphamide-induced diabetes in NOD mice. Diabetes Nutr Metab 5:61-63
314. Nicoletti F, Borghi MO, Meroni PL, Barcellini W, Fain C, Di Marco R, Menta R, Schorlemmer HU, Bruno G, Magros G, Grasso S 1992 Prevention of cyclophosphamide-induced diabetes in the NOD/WEHI mouse with deoxyspergualin. Clin Exp Immunol 91:232-236
315. Baeder WL, Sredy J, Sehgal SN, Chang JY, Adams LM 1992 Rapamycin prevents the onset of insulin-dependent diabetes mellitus (IDDM) in NOD mice. Clin Exp Immunol 89:174-178
316. Hayward AR, Schriber M, Cooke A, Waldmann H 1993 Prevention of diabetes but not insulitis in NOD mice injected with antibody to CD4. J Autoimmun 6:301-310
317. Wang Y, Hao L, Gill RG, Lafferty KJ 1987 Autoimmune diabetes in NOD mouse is L3T4 T-lymphocyte dependent. Diabetes 36:535-538
318. Koike T, Itoh Y, Ishii T, Ito I, Takabayashi K, Maruyama N, Tomioka H, Yoshida S 1987 Preventive effect of monoclonal antiL3T4 antibody on development of diabetes in NOD mice. Diabetes 36:539-541
319. Shizuru JA, Taylor-Edwards C, Banks BA, Gregory AK, Fathman CG 1988 Immunotherapy of the nonobese diabetic mouse: treatment with an antibody to T-helper lymphocytes. Science 240:659-662
320. Hutchings PR, Simpson E, O’reilly LA, Lund T, Waldmann H, Cooke A 1990 The involvement of Ly2+ T cells in beta cell destruction. J Autoimmun 3 [Suppl 1]:101-109
321. Taki T, Nagata M, Ogawa W, Hatamori N, Hayakawa M, Hari J, Shii K, Baba S, Yokono K 1991 Prevention of cyclophosphamide-induced and spontaneous diabetes in NOD/Shi/Kbe mice by anti-MHC class I Kd monoclonal antibody. Diabetes 40:1203-1209
322. Kelley VE, Gaulton GN, Hattori M, Ikegami H, Eisenbarth G, Strom TB 1988 Anti-interleukin 2 receptor antibody suppresses murine diabetic insulitis and lupus nephritis. J Immunol 140: 59-61
323. Pacheco-Silva A, Bastos MG, Muggia RA, Pankewycz O, Nichols J, Murphy JR, Strom TB, Rubin-Kelley VE 1992 Interleukin 2 receptor targeted fusion toxin (DAB486-IL-2) treatment blocks diabetogenic autoimmunity in non-obese diabetic mice. Eur J Immunol 22:697-702
324. Rabinovitch A, Suarez WL, Power RF 1992 Combination therapy with an antioxidant and a corticosteroid prevents autoimmune diabetes in NOD mice. Life Sci 51:1937-1943
325. Mathieu C, Laureys J, Sobis H, Vandeputte M, Waer M, Bouillon R 1992 1, 25-Dihydroxyvitamin D3 prevents insulitis in NOD mice. Diabetes 41:1491-1495
326. Wilberz S, Herberg L, Renold AE 1988 Gangliosides in vivo reduce diabetes incidence in non-obese diabetic mice. Diabetologia 31:855-857
327. Pearce RB, Peterson CM 1991 Studies of concanavalin A in nonobese diabetic mice. I. Prevention of insulin-dependent diabetes. J Pharmacol Exp Ther 258:710-715
328. Yamada K, Nonaka K, Hanafusa T, Miyazaki A, Toyoshima H, Tarui S 1982 Preventive and therapeutic effects of large-dose nicotinamide injections on diabetes associated with insulitis. An observation in nonobese diabetic (NOD) mice. Diabetes 31: 749-753
329. Forsgren S, Andersson A, Hillorn V, Soderstrom A, Holmberg D 1991 Immunoglobulin-mediated prevention of autoimmune diabetes in the non-obese diabetic (NOD) mouse. Scand J Immunol 34:445-451
330. Charlton B, Bacelj A, Mandel TE 1988 Administration of silica particles or anti-Lyt2 antibody prevents beta-cell destruction in NOD mice given cyclophosphamide. Diabetes 37:930-935
331. Like AA, Kislauskis E, Williams RR, Rossini AA 1982 Neonatal thymectomy prevents spontaneous diabetes mellitus in the BB/W rat. Science 216:644-646
332. Laupacis A, Stiller CR, Gardell C, Keown P, Dupre J, Wallace AC, Thibert P 1983 Cyclosporin prevents diabetes in BB Wistar rats. Lancet 1:10-12
333. Jaworski MA, Honoré L, Jewell LD, Mehta JG, McGuire-Clark P, Schouls JJ, Yap WY 1986 Cyclosporin prophylaxis induces long-term prevention of diabetes, and inhibits lymphocytic infiltration in multiple target tissues in the high-risk BB rat. Diabetes Res 3:1-6
334. Like AA, Dirodi V, Thomas S, Guberski DL, Rossini AA 1984 Prevention of diabetes mellitus in the BB/W rat with CydosporinA. Am J Pathol 117:92-97
335. Like A A, Rossini A A, Guberski DL, Appel MC, Williams RM 1979 Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Srience 206:1421-1423
336. Boitard C, Michie S, Serrurier P, Butcher GW, Larkins AP, McDevitt HO 1985 In vivo prevention of thyroid and pancreatic autoimmunity in the BB rat by antibody to class II major nistocompatibility complex gene products. Proc Natl Acad Sd USA 82:6627-6631
337. Rossini AA, Slavin S, Woda BA, Geisberg M, Like AA, Mordes JP 1984 Total lymphoid irradiation prevents diabetes mellitus in the Bio-Breeding/Worcester (BB/W) rat. Diabetes 33:543-547
338. Satoh J, Seino H, Shintani S, Tanaka S, Ohteki T, Masuda T, Nobunaga T, Toyota T 1990 Inhibition of type 1 diabetes in BB rats with recombinant human tumor necrosis factor-alpha. J Immunol 145:1395-1399
339. Vialettes B, Picq R, Du Rostu M, Charbonnel B, Rodier M, Mirouze J, Vexiau P, Passa P, Pehuet M, Elgrably F, Vague P 1990 A preliminary multicentre study of the treatment of recently diagnosed type 1 diabetes by combination nicotinamide-cyclosporin therapy. Diabetic Med 7:731-735
340. Atkison PR, Mahon JL, Dupre J, Stiller CR, Jenner MR, Paul TL, Momah Cl 1990 Interaction of bromocriptine and cyclosporine in insulin dependent diabetes mellitus: results from the Canadian open study. J Autoimmun 3:793-799
341. Carroll PB, Tzakis AG, Ricordi C, Rilo HR, Abu-El-Magd K, Murase N, Zeng YJ, Alejandro R, Mintz D, Starzl TE 1991 The use of FK 506 in new-onset type 1 diabetes in man. Transplant Proc 23:3351-3353
342. Secchi A, Pastore MR, Sergi A, Pontiroli AE, Pozza G 1990 Prednisone administration in recent onset type I diabetes. J Autoimmun 3:593-600
343. Moncada E, Subira ML, Oleaga A, Goni F, Sanchez-Ibarrola A, Monreal M, Sevilla M, Goni MJ, Yoldi A, Teran D, Llorente I 1990 Insulin requirements and residual beta-cell function 12 months after concluding immunotherapy in type I diabetic patients treated with combined azathioprine and thymostimulin administration for one year. J Autoimmun 3:625-638
344. Panto F, Giordano C, Amato MP, Pugliese A, Donatelli M, D’Acquisto G, Galluzzo A 1990 The influence of high dose intravenous immunoglobulins on immunological and metabolic pattern in newly diagnosed type I diabetic patients. J Autoimmun 3:587-592
345. Krug J, Verlohren HJ, Bierwolf B, Lampeter E, Borte M, Nietzschmann U, Haustein B, Lohmann D 1990 Lymphocyte transfusion in recent onset type I diabetes mellitus-a one-year follow-up of cell-mediated anti-islet cytotoxicity and C-peptide secretion. J Autoimmun 3:601-609
346. Dempe A, Baaske W, Von Baehr R, Kuttner S, Neubert G, Neumeister K 1988 Remission of the newly diagnosed type 1 diabetes by radiation of the pancreas. Exp Clin Endocrinol 92: 123-125
347. Giordano C, Pantoo F, Amato MP, Sapienza N, Pugliese A, Galluzzo A 1990 Early administration of an immunomodulator and induction of remission in insulin-dependent diabetes mellitus. J Autoimmun 3:611-617