The induction of operational tolerance is not prevented by simultaneous administration of cyclosporin A1.
In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival. The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced by anti-CD4 mAb therapy, 50% of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were used concurrently at the time of transplantation.
Hamano
K
K
First Department of Surgery, Yamaguchi University, School of Medicine, Japan.
Ito
H
H
Bushell
A
A
Wood
K J
KJ
Esato
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015704:CD4 Antigens / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology*; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016572:Cyclosporine