Transgenic mice expressing constitutive levels of IL-2 in islet beta cells develop diabetes.
IL-2 plays an important role in the clonal expansion of T cells during an immune response and it has been implicated in autoimmune disease. To examine the role of IL-2 in the regulation of peripheral tolerance we produced transgenic mice in which the expression of murine IL-2 was directed by the rat insulin II promoter. The IL-2 transgene was expressed specifically in the pancreas. Islets from transgenic mice synthesized biologically active IL-2. Expression of IL-2 in the pancreas resulted in a massive inflammatory response directed at the beta cells of the pancreas. The infiltrate consisted primarily of B cells and CD4+ and CD8+ T cells. The infiltrate resulted in destruction of the insulin-producing beta cells and diabetes, but there was no evidence for antigen specificity. The results suggest that local IL-2 production elicits the recruitment and activation of cells capable of destroying beta cells by non-antigen-specific mechanisms.
Elliott
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EA
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510.
Flavell
R A
RA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005934:Glucagon / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D007124:Immunoenzyme Techniques; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic
D007376:Interleukin-2; D005934:Glucagon; D005947:Glucose