Induction of prolonged tolerance to third-party skin grafts following fully allogeneic bone marrow transplantation in mice.

Fully allogeneic C57BL/6-->BALB/c chimeras were grafted at different intervals after bone marrow transplantation with C3H/HeJ skin grafts. We found that the donor-type and host-type skin grafts were always permanently accepted by the allogeneic chimeras, whereas the acceptance or rejection of third-party grafts was dependent on the timing of skin grafting: if grafted later then 3.5 weeks after BMT, they were rejected; if grafted earlier they were accepted for prolonged periods (over 100 days). We further show that 77% of the C57BL/6-->BALB/c chimeras that had been grafted with C3H/HeJ skin within the first 2 weeks post-BMT were still holding the graft 15 weeks after transplantation, as opposed to 11% of the chimeras that had been grafted 8.5 weeks post-BMT. Syngeneic BALB/c-->BALB/c chimeras, in contrast to allogeneic chimeras, promptly rejected the third-party skin grafts even when these grafts were placed within the first 3 weeks after BMT. Thymocytes and splenocytes from allogeneic chimeras that accepted the third-party skin grafts were able to mount relatively strong mixed lymphocytes reactions against the third-party antigens. Grafting of secondary skin grafts from the third-party donor on chimeras that had already accepted such skin grafts led to a prompt rejection of both third-party grafts but not of donor-type skin grafts, suggesting that the immune capacity to reject third-party skin grafts has already been attained in such chimeras. It is therefore suggested that the prolonged tolerance to third-party skin grafts may be associated with the origin of the bone marrow--derived cells in the skin graft.