SPONTANEOUS REESTABLISHMENT OF SELF-TOLERANCE IN BB PFD RATS/

We describe a substrain of BB rats, BB/Pfd, characterized by a loss of autoimmune potential soon after onset of diabetes. When fresh syngene ic (BB/Pfd) islets (6 islets/g body weight) were transplanted under th e kidney capsule of diabetic BB/Pfd rats 1-2 weeks after diabetes onse t (n=14), no recurrence of diabetes occurred. When, however, islets we re transplanted on the day of diabetes diagnosis (n=16), 10 animals we re able to destroy the transplant (P<0.005 vs. previous group). Pancre atic biopsies taken at the moment of transplantation in both groups sh owed an almost complete disappearance of beta cells and also insulitis in the pancreata of the 1- to 2-week diabetic rats, while the acutely diabetic rats still conserved a certain amount of beta cells and a fl orid insulitis. The development of a general immune defect was not the cause of this nonrecurrence, since allogeneic islet grafts were easil y rejected (7 of 8), nor was there a general defect in mounting immune memory, since second set skin grafts could be rejected in an accelera ted manner (9.7 vs. 15.8 days). The development of suppressor mechanis ms as cause for nonrecurrence could not be demonstrated, since transfe r of lymphocytes taken from 1- to 2-week diabetic rats into acutely di abetic rats at the moment of syngeneic islet transplantation was unabl e to prevent recurrence of disease (6 recurrences in 10 animals). We c onclude that in the BB/Pfd substrain, the autoimmune capacity wanes ra pidly after the onset of diabetes. This loss of autoimmune potential i s parallelled by a disappearance of insulitis in the native pancreas, but the exact mechanisms of the spontaneous reestablishment of self-to lerance remain unclear.