Posttransplant administration of donor leukocytes induces long-term acceptance of kidney or liver transplants by an activation-associated immune mechanism

Donor leukocytes play a dual role in rejection and acceptance of transplant ed organs. They provide the major stimulus for rejection, and their removal from the transplanted organ prolongs its survival. Paradoxically, administ ration of donor leukocytes also prolongs allograft survival provided that t hey are administered 1 wk or more before transplantation. Here we show that administration of donor leukocytes immediately after transplantation induc ed long-term acceptance of completely MHC-mismatched rat kidney or liver tr ansplants. The majority of long-term recipients of kidney transplants were tolerant of donor-strain skin grafts. Acceptance was associated with early activation of recipient T cells in the spleen, demonstrated by a rapid incr ease in IL-2 and IFN-gamma at that site followed by an early diffuse infilt rate of activated T cells and apoptosis within the tolerant grafts. In cont rast, IL-2 and IFN-gamma mRNA were not increased in the spleens of rejectin g animals, and the diffuse infiltrate of activated T cells appeared later b ut resulted in rapid graft destruction. These results define a mechanism of allograft acceptance induced by donor leukocytes that is associated with a ctivation-induced cell death of recipient T cells. They demonstrate for the first time that posttransplant administration of donor leukocytes leads to organ allograft tolerance across a complete MHC class I plus class II barr ier, a finding with direct clinical application.