A role for nonspecific (cyclosporin A) or specific (monoclonal antibodies to ICAM-1, LFA-1, and IL-10) immunomodulation in the prolongation of skin allografts after antigen-specific pretransplant immunization or transfusion.

C3H/HEJ mice given pretransplant immunization via the portal vein with irradiated B10.BR spleen cells or non-irradiated B10.BR peripheral blood leukocytes showed delayed rejection of B10.BR but not BALB.K skin grafts. No increased graft survival was seen if pretransplant immunization was given by the lateral tail vein. Addition of a single treatment with cyclosporin A after pretransplant immunization via the portal vein led to indefinite graft survival in over 70% of recipients. As reported earlier, increased graft survival in vivo was correlated with preferential production of IL-4 (from Th2 type cells) rather than IL-2 from lymphocytes stimulated in vitro. When mice were given pretransplant transfusion via the lateral tail vein and a combination of anti-LFA-1 and anti-ICAM-1 mAbs, increased graft survival was again seen. In addition, in vivo injection of anti-IL-10 mAbs (but not anti-IFN-gamma or anti-IL-4 mAbs) abolished the delayed rejection seen when mice received pretransplant immunization via the portal vein. In all cases, delayed graft rejection in vivo was correlated with preferential activation of Th2-type cells, as assessed by lymphokine production from cells harvested from treated mice and activated in vitro.