Immunosuppressive antibody treatment prolongs graft survival in two murine models of segmental pancreas transplantation

Abstract

Successful pancreas transplantation requires the suppression of both allograft rejection and recurrence of autoimmune disease. In order to study treatments to suppress these two responses, separate models were developed for pancreas allograft rejection and autoimmune disease. In the first model, the diabetic state was induced with streptozotocin in CBA mice prior to the transplantation of pancreas grafts from BALB/c donors. In the absence of autoimmune disease, control mice rejected their grafts in 26 days (median). Antibody treatments (anti-lymphocyte serum and anti-CD4) significantly prolonged allograft survival beyond this time, but not to the extent we have previously reported in the heart graft model. NOD/Lt mice spontaneously developed autoimmune diabetes, and recurrence of disease was seen in isografts at 9.5 days (median). Antibody treatments significantly delayed disease recurrence, with anti-CD4 being the most effective. Heart allografts (CBA donors) in NOD/Lt recipients were rejected within 17 days (median), and the anti-CD4 treatment had a moderate effect in delaying graft survival (median 28 days). Anti-lymphocyte serum did not prolong graft survival. Thus antibody treatment was effective in delaying both rejection and the recurrence of autoimmune disease in segmental pancreas grafts. However, the same doses were not effective in delaying heart rejection in the NOD/Lt model, so it would appear that treatments which inhibit autoimmune disease may not prevent allograft rejection.