Abstract
INSULIN-DEPENDENT diabetes mellitus is widely believed to be an autoimmune disease1. Recent onset diabetics show destruction of insulin-secreting pancreatic β -cells associated with a lymphocytic infiltrate (insulitis) 2, with autoantibodies to β-cells being found even before the onset of symptoms3. Susceptibility to the disease is strongly influenced by major histocompatibility complex (MHC) class II polymorphism in both man4 and experimental animal models such as the non-obese diabetic (NOD) mouse5. As MHC class II molecules are usually associated with dominant immune responsiveness, it was surprising that introduction of a transgenic class II molecule, I–E, protected NOD mice from insulitis and diabetes6. This could be explained by a change either in the target tissue or in the T cells presumed to be involved in β-celI destruction. Recently, several studies have shown that I–E molecules are associated with ontogenetic deletion of T cells bearing antigen/MHC receptors encoded in part by certain T-cell receptor Vβ gene segments7–11. To determine the mechanism of the protective effect of I–E, we have produced cloned CD4+ and CD8+ T-cell lines from islets of recently diabetic NOD mice. These cloned lines are islet-specific and pathogenic in both I–E− and I–E+ mice. Both CD4+ and CD8+ cloned T cells bear receptors encoded by a Vβ5 gene segment, known to be deleted during development in I–E expressing mice10. Our data provide, therefore, an explanation for the puzzling effect of I–E on susceptibility to diabetes in NOD mice.
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Reich, EP., Sherwin, R., Kanagawa, O. et al. An explanation for the protective effect of the MHC class II I–E molecule in murine diabetes . Nature 341, 326–328 (1989). https://doi.org/10.1038/341326a0
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DOI: https://doi.org/10.1038/341326a0
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