Specific Immunosuppression for Fetal Pancreas Allografts in Rats

This paper is a review of our current work, evaluating the effectiveness of specific immunosuppressive treatment for prolongation of rat fetal pancreas allo-graft survival. Passively given antidonor antibodies that markedly prolong kidney and heart allograft survival had little effect on allogeneic whole fetal pancreases grafted onto the subcapsular space of the kidney. In contrast, the combination of pretreatment with donor antigen followed by procarbazine hydrochloride (PCH) and antilymphocyte serum (ALS) had a marked effect on fetal pancreas survival. The efficacy of the treatment increased when allograft incompatibility was smaller. Thus, a single injection of both PCH and ALS induced lifelong unresponsiveness to Lewis (LEW) fetal pancreases in 80% of Fischer (F344) recipients across this weak, non-H-1 incompatibility. These allografts were fully functional and completely reversed the host diabetes. Specificity of unresponsiveness was confirmed by prolonged survival of donor-type skin but acute rejection of third-party skin allografts on these recipients. Fetal pancreases surviving more than 300 days in an allogeneic recipient were fully capable of eliciting a rejection reaction in a secondary recipient. When the immunogenetic barrier was greater, stronger immunosuppressive treatment was necessary. In intermediate incompatibility, F344 to LEW, and strong H-1 incompatibility, (LEW x BUF) F1 to LEW, a total of 8–10 injections of PCH and ALS given on alternate days was needed to extend pancreas survivals from 14 days, characteristic of the controls, to 50–70 days with substantial improvement of the host diabetes. Additional approaches for increasing the efficacy of immunosuppressive treatment are discussed.