Lack of recurrence of insulin-dependent diabetes mellitus in syngeneic and allogeneic islet-transplanted diabetic biobreeding rats.

Abstract

Previous reports on experimental islet transplantation in animal models of human insulin-dependent diabetes mellitus show that islet grafts are susceptible to autoimmune destruction similar to that seen in native pancreatic islets. In this study, we demonstrated a lack of disease recurrence in diabetic BioBreeding (BB) rats after syngeneic and allogeneic islet transplantation. Four hundred to 1200 islets from BB (RT1u) and Lewis (RT1(1)) donors, isolated with stationary collagenase digestion and Ficoll density purification, were intraportally transplanted into spontaneously diabetic BB rats. The recipients received no immunologic manipulations before or after islet transplantation. When more than 900 syngeneic islets or when more than 600 allogeneic islets were transplanted, BB recipients remained normoglycemic for over 280 days, irrespective of age at onset, duration of exogenous insulin treatment, or age at transplantation. When at least 500 islets were transplanted, the recipients survived for a long period with normoglycemia or in a noninsulin-dependent diabetic state. Upon histological examination, mononuclear cell infiltration was observed in every islet graft examined, but the severity of infiltration in most of the grafts was mild to moderate. These results indicate that the islet grafts in the BB recipients were destroyed extremely slowly. It is conceivable that in our BB colony, a state of immunologically low responsiveness that allows diabetic animals to accept syngeneic or allogeneic islet grafts, occurs around the onset period and becomes more pronounced with aging. Our BB rat colony can be considered to be a novel substrain with unique immunological characteristics.