Posttransplant administration of donor leukocytes induces long-term acceptance of kidney or liver transplants by an activation-associated immune mechanism
Yq. Yan et al., Posttransplant administration of donor leukocytes induces long-term acceptance of kidney or liver transplants by an activation-associated immune mechanism, J IMMUNOL, 166(8), 2001, pp. 5258-5264
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.