Autoimmune Destruction of Islets Transplanted Into RT6-Depleted Diabetes-Resistant BB/Wor Rats

Peter A Gottlieb; Javier P Berrios; Gabriella Mariani; Eugene S Handler; Dale Greiner; John P Mordes; Aldo A Rossini

doi:10.2337/diab.39.5.643

Rapid Publications

Autoimmune Destruction of Islets Transplanted Into RT6-Depleted Diabetes-Resistant BB/Wor Rats

Peter A Gottlieb,
Javier P Berrios,
Gabriella Mariani,
Eugene S Handler,
Dale Greiner,
John P Mordes and
Aldo A Rossini

Department of Medicine, University of Massachusetts Medical School Worcester, Massachusetts Department of Pathology, University of Connecticut Health Center Farmington, Connecticut

Address correspondence and reprint requests to Aldo A. Rossini, MD, Diabetes Division, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655.

Diabetes 1990 May; 39(5): 643-645. https://doi.org/10.2337/diab.39.5.643

Abstract

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, <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.