INDUCTION OF SMALL BOWEL TRANSPLANTATION TOLERANCE BY DONOR-SPECIFIC BONE MARROW TRANSPLANTATION

Abstract

Immune response after allogeneic small bowel transplantation is more vigorous compared to other organ transplantations. It is often difficult to control small bowel allograft rejection with conventional immunosuppressive therapy. While many experimental studies showed organ transplantation tolerance, there have been few reports of tolerance in allogeneic small bowel transplantation. Induction of bone marrow chimerism is a potent strategy of tolerance induction. We tried to induce tolerance in SBT using donor-specific bone marrow transplantation (BMT) with cyclophosphamide (CYP) and tacrolimus. BN and LEW rats were used as donors and recipients. LEW recipients received BMT from BN donors after injection of CYP. The recipients were further treated with 0.3 mg/kg/day tacrolimus on days 0-6 (n=5). Establishment of bone marrow chimerism in BMT recipients was evaluated by flowcytometry of peripheral blood mononuclear cells. These recipients received small bowel transplantation from BN donors on day 100 after BMT. All of these recipients accepted BN small bowel allografts indefinitely (＞100 days), while untreated LEW controls rejected BN grafts within 8 days (n=6). Histologic signs of chronic rejection were not observed in small bowel allografts in these recipients. In conclusion, donor-specific BMT with a single dose of CYP and a short course of tacrolimus in the early phase successfully induced small bowel transplant tolerance across MHC-barriers. This strategy may lead to technical innovation of immuno- suppressive treatment in clinical small bowel transplantation.