Petersson E, Qi Z, Hedlund G, Ekberg H
The Wallenberg Laboratory, Lund University, Lund, Sweden.
Cell Immunol. 1998 Oct 10;189(1):19-24. doi: 10.1006/cimm.1998.1353.
Permanent graft acceptance was induced with cyclosporine A in a low responder rat strain combination PVG (RT1(c)) to DA (RT1(av1)) of cardiac transplants. Challenge (alloimmunization) with donor and third-party WF (RT1(u)) 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 activation in vivo the recipients failed to reject their established grafts, implying an ongoing presence of suppression.
