ELIMINATION OF ACUTE GVHD AND PROLONGATION OF RAT PANCREAS ALLOGRAFT SURVIVAL WITH DST, CYCLOSPORINE, AND SPLEEN TRANSPLANTATION

Abstract

Allogeneic spleen transplantation has been shown to have a tolerizing effect on pancreas allograft survival in rats. In this study we examined the effect of blood transfusions and cyclosporine administration on both rat pancreas allograft survival and acute graft-versus-host disease in BN recipients of Lewis pancreas-spleen allografts. We found that in this strain combination significant pancreas allograft prolongation occurred when the spleen was included en bloc with the pancreas graft. However, 50% of these recipients developed GVHD and died. A single donor-specific transfusion delivered to BN recipients of Lewis pancreas and pancreas-spleen allografts did not extend graft survival, but precluded the development of GVHD. A short, 6-day, and long, 26-day, course of CsA to recipients of pancreas and pancreas-spleen allografts extended graft and animal survival times, although not indefinitely. All pancreas-spleen recipients of both CsA protocols died following acute GVHD. Combined DST and CsA (short and long-course) administration in pancreas-only allograft recipients was deleterious to graft survival, compared with CsA administration alone. However, in pancreas-spleen recipients, combined DST and CsA had an additive effect. Moreover, in DST and long-course CsA-treated pancreas-spleen recipients, indefinite graft survival occurred with no signs of acute GVHD. The beneficial effect of the spleen allograft on pancreas graft survival was not dependent upon GVHD, since splenic-induced prolongation of pancreas graft survival was observed in the F1-donor to parent-recipient combination.