PREVENTION OF AUTOIMMUNE ISLET ALLOGRAFT DESTRUCTION BY ENGRAFTMENT OF DONOR T-CELLS

The results of clinical islet transplantation have remained poor when compared with the consistent success of pancreas transplantation. Auto immunity has usually been discounted as a cause of islet transplant fa ilure, Previously, we demonstrated that pancreas transplants from the diabetes resistant BB rat (BB-DR) function indefinitely in autoimmune diabetic hosts, but islets from the same donor are vulnerable to recur rent autoimmunity, Addition of 100 million pancreatic lymph node cells (PLNC) to BE-DR islets restores resistance to autoimmunity and leads to repletion of a T cell subset (RT6.1) in the recipients. Autoimmune (BB-Ac) and streptozocin (BB-Sz) diabetic BE rats were recipients of W istar Furth (WF) intraportal islet or islets plus PLNC transplants wit h cyclosporine 5 mg/kg/day recipient treatment. One cohort of Brown No rway (BN) islet transplants to BB-Ac with CsA was performed. At the te rmination of the experiment, recipient peripheral blood lymphocytes (P BL) were characterized by flow cytometry (FACS) for class I, CD4, CD8, RT6.1, and RT6.2, a T cell maturation marker found in WF but not BE r ats. All (14/14) WF and 75% (6/8) BN islet transplants to BB-Ac recipi ents failed after a mean of 42 and 36 days, respectively, despite CsA immunosuppression. WF islets were successful in 6/8 (75%) transplants to BB-Sz recipients (P<0.001 vs, BB-Ac recipients), confirming that au toimmunity is the major cause of islet failure in BB-Ac rats. Addition of PLNC to WF islets increased the survival in BB-Ac to 82% (9/11) (P <0.0001 vs. WF islets alone). Recipients of islet + PLNC express 19.7% RT6.2 compared with 4.6% and 4.0% for WF islets alone in BB-Ac (P<0.0 1) and BB-Sz (P<0.01), respectively. Autoimmunity is an important fact or leading to islet transplant failure in autoimmune diabetic BB rats, Addition of donor PLNC prevent islet allograft failure and leads to r ecipient chimerism for a donor T cell subset (RT6.2) associated with r esistance to autoimmunity.