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Type 1 diabetes mellitus: an imbalance between effector and regulatory T cells?

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Abstract

Abundant evidence now exists that autoimmunity plays a critical role in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus. The non-obese diabetic (NOD) mouse is an extensively studied animal model of this T-cell-mediated autoimmune disease. Our laboratory has focused on isolating diabetogenic T cell clones from NOD mice as a means of elucidating the pathogenesis of type 1 diabetes. This experimental approach presupposes that type 1 diabetes in NOD mice results from the action of islet-reactive T cells that are not present in other mouse strains; the diabetogenic T cells would therefore represent “forbidden clones” which exist in NOD mice as a result of a failure of clonal deletion. While the inappropriate presence of diabetogenic T cells probably play a central role in murine diabetes, it cannot explain all aspects of the disease. Type 1 diabetes is a chronic disorder with a lengthy preclinical stage; if the diabetogenic T cells acted in an unopposed fashion, one might expect to see a much more fulminant clinical course. This observation suggests that regulatory influences are likely to exist in this disease —a possibility supported by recent experimental data. If these regulatory influences could be identified and enhanced, specific immunotherapy for type 1 diabetes could be achieved.

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  1. Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, Fitkin I, Box 3333, 06510, New Haven, Connecticut, USA

    E. J. Rashba, E. -P. Reich, C. A. Janeway & R. S. Sherwin

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  1. E. J. Rashba
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  2. E. -P. Reich
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  3. C. A. Janeway
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  4. R. S. Sherwin
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Rashba, E.J., Reich, E.P., Janeway, C.A. et al. Type 1 diabetes mellitus: an imbalance between effector and regulatory T cells?. Acta Diabetol 30, 61–69 (1993). https://doi.org/10.1007/BF00578215

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