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 (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.
Petersson
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The Wallenberg Laboratory, Lund University, Lund, Sweden. Eva.Petersson@wblab.lu.se
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Hedlund
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Ekberg
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D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D007166:Immunosuppressive Agents; D016572:Cyclosporine