LACK OF RECURRENCE OF INSULIN-DEPENDENT DIABETES-MELLITUS IN SYNGENEIC AND ALLOGENEIC ISLET-TRANSPLANTED DIABETIC BIOBREEDING RATS

Background. Previous reports on experimental islet transplantation in animal models of human insulin-dependent diabetes mellitus show that i slet grafts are susceptible to autoimmune destruction similar to that seen in native pancreatic islets, In this study, we demonstrated a lac k of disease recurrence in diabetic Bio-Breeding (BB) rats after synge neic and allogeneic islet transplantation. Methods, Four hundred to 12 00 islets from BE (RT1(u)) and Lewis (RT1(1)) donors, isolated with st ationary collagenase digestion and Ficoll density purification, were i ntraportally transplanted into spontaneously diabetic BE rats. The rec ipients received no immunologic manipulations before or after islet tr ansplantation, Results, When more than 900 syngeneic islets or when mo re than 600 allogeneic islets were transplanted, BE recipients remaine d normoglycemic for over 280 days, irrespective of age at onset, durat ion of exogenous insulin treatment, or age at transplantation. When at least 500 islets were transplanted, the recipients survived for a lon g period with normoglycemia or in a noninsulin-dependent diabetic stat e. Upon histological examination, mononuclear cell infiltration was ob served in every islet graft examined, but the severity of infiltration in most of the grafts was mild to moderate. These results indicate th at the islet grafts in the BE recipients were destroyed extremely slow ly. Conclusions. It is conceivable that in our BE colony, a state of i mmunologically low responsiveness that allows diabetic animals to acce pt syngeneic or allogeneic islet grafts, occurs around the onset perio d and becomes more pronounced with aging. Our BE rat colony can be con sidered to be a novel substrain with unique immunological characterist ics.