THE INDUCTION OF OPERATIONAL TOLERANCE IS NOT PREVENTED BY SIMULTANEOUS ADMINISTRATION OF CYCLOSPORINE-A

In this study, the effect of combining anti-CD4 monoclonal antibody (m Ab) and cyclosporin (CyA) therapy at the time of transplantation was e xamined. A mouse cardiac allograft model was used. Anti-CD4 mAb admini stered perioperatively induces long-term survival. The addition of a s hort course of CyA given subcutaneously in a regimen of either a high- dose treatment or a standard dose treatment to the anti-CD4 mAb treatm ent protocol did not have a detrimental effect on graft survival. Desp ite having no significant effect on graft survival, the addition of Cy A to the treatment protocol did result in a significant decrease in th e level of IL-2 present in the hearts 7 days after transplantation. Th e decrease in IL-2 production was directly related to the presence of CyA in vivo. When CyA treatment was continued throughout the period du ring which unresponsiveness to the graft is induced by anti-CD4 mAb th erapy, 50 % of the grafted hearts were rejected once the CyA was disco ntinued. In conclusion, the combined use of anti-CD4 mAb therapy and C YA did not have a negative effect on graft survival in this model when the two agents were used concurrently at the time of transplantation.