The role of lymphocyte subsets in accelerated diabetes in nonobese diabetic-rat insulin promoter-B7-1 (NOD-RIP-B7-1) mice.
B7-1 transgene expression on the pancreatic islets in nonobese diabetic (NOD) mice leads to accelerated diabetes, with >50% of animals developing diabetes before 12 wk of age. The expression of B7-1 directly on the pancreatic beta cells, which do not normally express costimulator molecules, converts the cells into effective antigen-presenting cells leading to an intensified autoimmune attack. The pancreatic islet infiltrate in diabetic mice consists of CD8 T cells, CD4 T cells, and B cells, similar to diabetic nontransgenic NOD mice. To elucidate the relative importance of each of the subsets of cells, the NOD-rat insulin promoter (RIP)-B7-1 animals were crossed with NOD.beta2microglobulin -/- mice which lack major histocompatibility complex class I molecules and are deficient in peripheral CD8 T cells, NOD.CD4 -/- mice which lack T cells expressing CD4, and NOD.muMT -/- mice which lack B220-positive B cells. These experiments showed that both CD4 and CD8 T cells were necessary for the accelerated onset of diabetes, but that B cells, which are needed for diabetes to occur in normal NOD mice, are not required. It is possible that B lymphocytes play an important role in the provision of costimulation in NOD mice which is unnecessary in the NOD-RIP-B7-1 transgenic mice.
Wong
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Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. susan.wong@yale.edu
Visintin
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Wen
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Granata
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Flavell
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Janeway
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D019264:Adoptive Transfer; D017668:Age of Onset; D000818:Animals; D017951:Antigen Presentation; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D015994:Incidence; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D016131:Lymphocyte Subsets; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000637:transplantation
D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D007328:Insulin