ACTIVATION OF DONOR-SPECIFIC CTL IN A TOLERANT RECIPIENT OF CARDIAC ALLOGRAFT

Permanent graft acceptance was induced with cyclosporine A in a low re sponder rat strain combination PVG (RT1(c)) to DA (RT1(av1)) of cardia c transplants. Challenge (alloimmunization) with donor and third-party WF (RT1(u)) cells was performed and followed by the analysis of allor eactive cytotoxicity. The cytotoxic T lymphocytes (CTL) from recipient s with permanently accepted cardiac grafts manifested cytolytic activi ty against third-party target cells but not against donor target cells . The findings demonstrated unresponsiveness to be donor-specific, i.e ., transplant tolerance peas present. This was verified by retransplan tation of the DA recipient with either a second PVG heart (which was a ccepted) or a third-party (WF) heart (which was rejected). Restoration of donor-specific CTL after injection of exogeneous interleukin (IL)- 2 concomitant with challenge showed that the donor-specific CTL were n ot depleted, but unable to be activated as a consequence of IL-2 defic iency. Despite donor-specific CTL activation in vivo the recipients fa iled to reject their established grafts, implying an ongoing presence of suppression. (C) 1998 Academic Press.