TY - JOUR
T1 - Short-Term Cyclosporine Therapy and Cotransplantation of Donor Splenocytes
T2 - Effects on Graft Rejection and Survival Rates in Pigs Subjected to Renal Transplantation
AU - Maestri, Marcello
AU - Rademacher, Johannes
AU - Gaspari, Annalisa
AU - Lenti, Luca M.
AU - Crespi, Stefania
AU - Cansolino, Laura
AU - Novelli, Giuseppe
AU - Agoglitta, Domenico
AU - Maffeis, Federica
AU - Ferrario di Tor Vajana, Antonjacopo
AU - Oldani, Graziano
AU - Dionigi, Paolo
PY - 2008/11
Y1 - 2008/11
N2 - 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.
AB - 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.
KW - antigen-presenting cells
KW - cyclosporine A
KW - dendritic cells
KW - donor-specific transfusion
KW - kidney transplant
UR - http://www.scopus.com/inward/record.url?scp=53249121791&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53249121791&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2008.01.028
DO - 10.1016/j.jss.2008.01.028
M3 - Article
C2 - 18561953
AN - SCOPUS:53249121791
VL - 150
SP - 100
EP - 109
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 1
ER -