Suppression of Rejection of Allogeneic Islet Tissue in the Rat

A variety of immunosuppressive agents was used to prevent rejection of allografts of isolated rat islets of Langerhans injected into the portal vein or spleen, of fetal pancreases placed beneath the kidney capsule, or of vascularized hemipancreases. The agents included antilymphocytic serum (ALS), cyclophosphamide, Cyclosporin A, azathioprine, prednisolone, and donor-specific antiserum. Prolonged tissue culture of fetal pancreas and implantation of xenogeneic neonatal rabbit pancreases in Nucleopore bags were also carried out with the aim of suppressing rejection. In the face of a strong histocompatibility barrier, (DA x Lewis) F1 to Lewis, neither azathioprine nor prednisolone prolonged islet survival, whereas cyclo-phosphamide and Cyclosporin A prolonged survival by several days. ALS was an effective agent, prolonging islet survival by 26–50 days. Passive enhancement with donor-specific antiserum was modestly effective in DA to Lewis, but much more effective in the heterozygous [(DA x Lewis) F1 to Lewis or DA] combination. Survival of fetal pancreas was most prolonged by ALS, especially (DA x Lewis) F1 to Lewis, with a median survival time of 45 days. In contrast, Cyclosporin A, passive enhancement, and culture for 21 days were ineffective. Cyclosporin A was significantly effective only in prolonging function of the vascularized pancreas for up to 28 days.