Activation of Donor-Specific CTL in a Tolerant Recipient of Cardiac Allograft

Permanent graft acceptance was induced with cyclosporine A in a low responder rat strain combination PVG (RT1c) to DA (RT1av1) of cardiac transplants. Challenge (alloimmunization) with donor and third-party WF (RT1u) cells was performed and followed by the analysis of alloreactive cytotoxicity. The cytotoxic T lymphocytes (CTL) from recipients with permanently accepted cardiac grafts manifested cytolytic activity against third-party target cells but not against donor target cells. The findings demonstrated unresponsiveness to be donor-specific, i.e., transplant tolerance was present. This was verified by retransplantation of the DA recipient with either a second PVG heart (which was accepted) 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 not depleted, but unable to be activated as a consequence of IL-2 deficiency. Despite donor-specific CTL activationin vivothe recipients failed to reject their established grafts, implying an ongoing presence of suppression.