Specific T-cell tolerance may be essential for successful xenotranspla
ntation in humans. Grafting of thymectomized, T cell-depleted normal m
ice with xenogeneic fetal pig thymus and liver (FP THY/LIV) tissue res
ults in the recovery of functional CD4 antigen-positive cells. We have
tested T-cell tolerance by skin grafting. Donor-matched pig skin surv
ived permanently (>200 days), whereas allogeneic mouse skin was rapidl
y rejected. Nontolerant control mice rejected pig skin within 26 days.
Both porcine and murine histocompatibility class IIhigh cells were de
tected in long-term thymus grafts, and T-cell repertoire analyses sugg
ested that tolerance to both donors and recipients developed, at least
in part, by intragraft clonal deletion. This study demonstrates the p
rinciple that tolerance, measured by the stringent criterion of skin g
rafting, can be induced across a widely disparate species barrier.