The role of MHC compatibility in recurrence of autoimmune type I diabetes mellitus: comparison of the immune response of BB/W rats to pancreatic islet and heart allografts.

Abstract

Human type I diabetes mellitus has been shown to be an autoimmune disease. The BioBreeding/Worcester (BB/W) rat is an excellent model of insulin dependent diabetes mellitus (IDDM). Using the spontaneous diabetic BB/W rats, autoimmune recurrence of diabetes mellitus was evaluated. To prevent allorejection of islets, a combination of ultraviolet B (UVB) donor islet pretreatment and brief peritransplant host immunosuppression with cyclosporine was utilized. Such combination led frequently to indefinite survival of MHC mismatched islets in the chronically diabetic BB/W recipients more than 15 days after onset of hyperglycemia, while MHC matched islets survived only briefly. The most likely reason for the relatively rapid loss of graft function of MHC matched islets is the autoimmune destruction by previously primed cells. The result of this study, together with the previous report of CHABOT et al that both MHC matched and MHC mismatched islets are destroyed in acutely diabetic BB/W rats (less than 15 days after onset) despite the use of UVB irradiation and cyclosporine, demonstrates that the initiation of autoimmune response toward islets is most likely MHC restricted. These results led to the conclusion that MHC matching may be contraindicated in future human pancreatic islet transplantation to avoid reactivation of the original autoimmune disease.