Autoimmune destruction of islets transplanted into RT6-depleted diabetes-resistant BB/Wor rats.
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.
Gottlieb
P A
PA
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.
Berrios
J P
JP
Mariani
G
G
Handler
E S
ES
Greiner
D
D
Mordes
J P
JP
Rossini
A A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015551:Autoimmunity; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D006084:Graft Rejection; D016381:Islets of Langerhans Transplantation; D007519:Isoantigens / Q000276:immunology; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014181:Transplantation Immunology / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007519:Isoantigens