Allogeneic small bowel transplantation with cyclosporine and donor whole-body irradiation

This study was designed to investigate the ability of CsA to prevent rejection and GVHD in a totally allogeneic transplant between two rat strains with strong histoincompatibility as well as to determine the utility of combining donor WBI as an adjunct to CsA treatment of the recipient. The results obtained in our study indicate that CsA is insufficient as single therapy for preventing allograft rejection in totally allogeneic small bowel transplantation. Donor WBI as an adjunct to CsA immunosuppression may be effective in preventing rejection in totally allogeneic small bowel transplantation by reducing the immunogenicity of the graft. The effectiveness of irradiation in reducing graft immunogenicity and preventing host sensitization is perhaps best explained by its ability to destroy or impair the MHC class II antigen-presenting cells carried within the grafted tissue and/or lymphocytes that effect enhanced class II MHC antigen expression on vascular endothelium through production of γ-interferon and interleukin 2. Provided that irradiation does not cause irreversible impairment of bowel function, adjunctive immunosuppressive therapy with donor WBI may provide a significant benefit in allowing lower initial doses of CsA followed by more rapid tapering. Reduced nonspecific immunosuppression of recipients may decrease the incidence of deleterious side effects, one of the most serious of which, as evidenced in this study, is fatal infection.