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Diabetes, Vol 39, Issue 5 643-645, Copyright © 1990 by American Diabetes Association

ARTICLES

Autoimmune destruction of islets transplanted into RT6-depleted diabetes-resistant BB/Wor rats

PA Gottlieb, JP Berrios, G Mariani, ES Handler, D Greiner, JP Mordes and AA Rossini
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.

We report a novel animal model of islet transplantation that distinguishes recurrence of autoimmunity from allograft rejection. In this study, diabetes-resistant (DR) BB rats, less than 1% of which develop spontaneous diabetes, were made hyperglycemic by either a single injection of streptozocin (STZ) or in vivo immune elimination of a regulatory T-lymphocyte subset that expresses the RT6 alloantigen. DR islet grafts were then transplanted into both groups. DR transplants into STZ-induced diabetic DR rats produced long-term normoglycemia. In contrast, DR transplants into DR rats that had been treated with anti-RT6 monoclonal antibody were all destroyed within an average of 4 days. Allogeneic islets transplanted into both STZ-induced and RT6-depleted diabetic DR rats were rejected within a mean of 3 days. We conclude that failure of DR islet grafts in RT6-depleted diabetic DR BB rats represents recurrent autoimmunity.
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