Characterization of xenograft resistance to autoimmune disease recurrence after pancreas islet transplantation.

AUTOIMMUNE disease recurrence (ADR) in pancreas islet grafts has been reported to cause a high percentage of all graft losses following islet transplantation in both experimental and clinical islet transplantation. This reaction is a predictable result of the reactivation of a pre-existing autoimmune process. Because autoimmune diseases involve a variety of immune mechanisms, most of which have been poorly characterized, and because immunosuppressive drugs do not block the process, treatment of this destructive process is difficult. In 1992, our group suggested that islet xenografts were highly resistant to ADR because porcine islets had a strikingly low incidence of ADR when transplanted into NOD mice, whereas allograft islets had a high incidence (70% to 80%) of ADR. Recently, our group transplanted xenograft islets into three primates all of whom are currently off immunosuppressive drugs for .6 months and without ADR. These results suggest that xenograft islets are highly resistant to ADR and the autoimmune disease state. In this study we attempted to further investigate the phenomenon of xenograft islets resistant to ADR and to focus further on this mechanism by comparing ADR in concordant (CI) and discordant donor islets (DI).