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

Marcello Maestri, Johannes Rademacher, Annalisa Gaspari, Luca M. Lenti, Stefania Crespi, Laura Cansolino, Giuseppe Novelli, Domenico Agoglitta, Federica Maffeis, Antonjacopo Ferrario di Tor Vajana, Graziano Oldani, Paolo Dionigi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)100-109
Number of pages10
JournalJournal of Surgical Research
Volume150
Issue number1
DOIs
Publication statusPublished - Nov 2008

Keywords

  • antigen-presenting cells
  • cyclosporine A
  • dendritic cells
  • donor-specific transfusion
  • kidney transplant

ASJC Scopus subject areas

  • Surgery

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