Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells.
Insulin-dependent diabetes is caused by the loss of insulin-producing beta cells in pancreatic islets. It has been proposed that aberrant expression of Class II Major Histocompatibility Complex (MHC) molecules on beta cells stimulates an autoimmune attack against beta cell antigens. To test this hypothesis, we generated transgenic mice that express Class II MHC molecules (E alpha d/E beta b, or I-Eb) on beta cells. Diabetes was found in 100% of transgenic progeny from three expressing transgenic mouse lines, but without evidence for lymphocytic infiltrates. Furthermore, T lymphocytes appeared to be tolerant to the transgene I-Eb molecule, despite the absence of expression of I-Eb in the thymus or any other lymphoid tissue. The results suggest that novel expression of Class II MHC molecules on nonlymphoid cells is by itself insufficient to initiate autoimmune responses against tissue-specific antigens.
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Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Burkly
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LC
Widera
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Cowing
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Flavell
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RA
Palmiter
R D
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Brinster
R L
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D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D006681:HLA-D Antigens / Q000235:genetics*; D007515:Islets of Langerhans / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
D006681:HLA-D Antigens; D012333:RNA, Messenger