Treatment with total lymphoid irradiation, cyclosporin A and a monoclonal anti-T-cell antibody in a hamster-to-rat heart transplantation model: Graft survival and morphological analysis

Abstract

Abstract. Treatment with preoperative total lymphoid irradiation and post-transplant cyclosporin A has been shown to have a synergistic effect on graft survival in alio-and xenotransplantation. Specific monoclonal antibodies against T cells and T cell subpopulations could offer new ways of preventing graft rejection in xenotransplantation. Graft survival and histology were examined after total lymphoid irradiation plus cyclosporin A treatment versus cyclosporin A plus a monoclonal antibody in a concordant, heterotopic, hamster-to-rat heart transplantation model. Preoperative total lymphoid irradiation was given at a dose of 1. 25 Gy, 12 times over a period of 3 weeks. Cyclosporin A at a dose of 12. 5 mg/kg per day was administered perorally and OX-19, a pan T cell monoclonal antibody, was given as intraperitoneal injections at doses of 100 μg or 500 μg/kg per day from day 0 until graft rejection. While total lymphoid irradiation alone prolonged graft survival to 9. 4 days, total lymphoid irradiation plus cyclosporin A extended graft survival to a mean of 22 days. Cyclosporin alone or combined with the monoclonal antibody could not increase graft survival significantly when compared to untreated animals, which rejected their grafts within 3. 7 days. Vascular rejection was the characteristic morphological finding, even after some weeks of excellent graft function. In conclusion, total lymphoid irradiation and cyclosporin A had a synergistic effect on graft survival in this concordant xenotransplantation model, although recent impressive results from other groups could not be reproduced. Total lymphoid irradiation combined with cyclosporin A appears to delay a primary humoral graft rejection, while the mechanism of rejection, judged by histology, stays the same.