Short-Term Cyclosporine Therapy and Cotransplantation of Donor Splenocytes: Effects on Graft Rejection and Survival Rates in Pigs Subjected to Renal Transplantation

Background Donor-specific allogeneic loading can prolong the survival of solid organ transplants by inducing a state known as acceptance. Several populations of cells are known to be involved in this process, but their exact roles have yet to be defined. The aim of this study was to assess the effects of portal-vein transfusion of donor-specific splenocytes (DST) after short-term cyclosporine A (CyA) therapy in pigs subjected to renal transplantation. Methods Four groups of unrelated swine underwent renal transplantation with removal of the native kidneys. Antirejection protocols consisted in portal-vein DST (3 × 108 cells/kg) (Group 2, n = 7); intravenous CyA (9 mg/kg/d) on postoperative days 1–12 (Group 3, n = 14); and DST + CyA (as described above) (Group 4, n = 13). Results (through postoperative day 90) were compared with those obtained in untreated control recipients (Group 1, n = 7). Results Compared with animals of Groups 1, 2, and 3, Group 4 recipients presented significantly longer survival (mean: 90 days, P < 0.01 in Kaplan-Meier analysis) and better renal function ( P < 0.05). Graft histology revealed preserved parenchyma. Conclusion The role of spleen cells in the immune response has probably been underestimated. Cotransplantation of donor splenocytes seems to induce a certain degree of acceptance toward the renal allograft. The route of administration (portal-vein infusion in this study) may be crucial for developing favorable mechanisms of recognition.