SKIN-GRAFT TOLERANCE ACROSS A DISCORDANT XENOGENEIC BARRIER

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.