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 x 10(8) 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.


CONCLUSIONS
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.
Laboratory of Experimental Surgery, Department of Surgical Sciences, University of Pavia, Pavia, Italy. mmaestri@smatteo.pv.it
Marcello
M
Maestri
Johannes
J
Rademacher
Annalisa
A
Gaspari
Luca M
LM
Lenti
Stefania
S
Crespi
Laura
L
Cansolino
Giuseppe
G
Novelli
Domenico
D
Agoglitta
Federica
F
Maffeis
Antonjacopo
A
Ferrario di Tor Vajana
Graziano
G
Oldani
Paolo
P
Dionigi
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000473:pathology; D013154:Spleen / Q000637:transplantation*; D013552:Swine
D007166:Immunosuppressive Agents; D016572:Cyclosporine