Concordant xenotransplantation - non-vascularized pancreatic islets are more difficult to regraft than the vascularized heart

We have previously demonstrated that it is possible to perform retransplant ation of a xenogeneic heart (mouse-to-rat) using cyclosporine A as monother apy, provided that the first heart is transplanted under a short course of deoxyspergualin (DSG). If DSG is omitted, the first heart is rejected withi n four days and the second heart succumbs to hyperacute rejection within mi nutes. A mouse heart as first graft does not protect a consecutive pancreat ic islet graft, although the heart continues to function after rejection of the cellular graft. One explanation for this discrepancy may be the fact t hat cellular grafts, as pancreatic islets, lack an endothelial lining. We h ave, therefore, further investigated possible differences between vasculari zed and nonvascularized xenografts regarding their capacity to induce unres ponsiveness. The use of pancreatic islets as primary graft neither accelerated nor decel erated the speed of rejection of the vascularized heart used as secondary g raft. Furthermore, hemagglutinating and cytotoxic antibody titres responded in the same manner as in naive rats transplanted with a mouse heart. Retra nsplantation with pancreatic islets also resulted in complete rejection of both the primary and secondary grafts. Thus, the lack of unresponsiveness c annot simply be explained by differences, between the pancreatic and cardia c tissues, in antigen expression. In addition, intraperitoneal transplantat ion of mouse heart cells as primary graft resulted in rejection of a second ary cardiac graft after three days. However, it cannot be totally excluded that the time of antigen exposure had an impact on these results. In conclusion, our previous and present studies suggest that the presence o f an intact vascular bed, both in the first and second graft, is necessary to create a state of unresponsiveness. Because the pancreatic islets lack a n endothelial lining, they do not benefit from an unresponsiveness of the i mmune system. Neither are they able to induce such an unresponsiveness.