TYPE-1 DIABETES-MELLITUS - AN IMBALANCE BETWEEN EFFECTOR AND REGULATORY T-CELLS

Abundant evidence now exists that autoimmunity plays a critical role i n the pathogenesis of type 1 (insulin-dependent) diabetes mellitus. Th e non-obese diabetic (NOD) mouse is an extensively studied animal mode l of this T-cell-mediated autoimmune disease. Our laboratory has focus ed on isolating diabetogenic T cell clones from NOD mice as a means of elucidating the pathogenesis of type 1 diabetes. This experimental ap proach pre-supposes that type 1 diabetes in NOD mice results from the action of islet-reactive T cells that are not present in other mouse s trains; the diabetogenic T cells would therefore represent ''forbidden clones'' which exist in NOD mice as a result of a failure of clonal d eletion. While the inappropriate presence of diabetogenic T cells prob ably plays a central role in murine diabetes, it cannot explain all as pects of the disease. Type 1 diabetes is a chronic disorder with a len gthy preclinical stage; if the diabetogenic T cells acted in an unoppo sed fashion, one might expect to see a much more fulminant clinical co urse. This observation suggests that regulatory influences are likely to exist in this disease - a possibility supported by recent experimen tal data. If these regulatory influences could be identified and enhan ced, specific immunotherapy for type 1 diabetes could be achieved.