IN-VIVO STUDIES OF THE MAINTENANCE OF PERIPHERAL TRANSPLANT TOLERANCEAFTER CYCLOSPORINE - RADIOSENSITIVE ANTIGEN-SPECIFIC SUPPRESSOR CELLSMEDIATE LASTING GRAFT PROTECTION AGAINST PRIMED EFFECTOR-CELLS

Cellular mechanisms responsible for maintenance of peripheral transpla nt tolerance in a rodent model were evaluated. Donor-specific toleranc e was established in ACI rats given a vascularized heterotopic cardiac allograft followed by a 10-day course of cyclosporine, Tolerance was associated with a reduction in donor-specific cytotoxic T lymphocyte p recursors and the presence within the spleen of cells capable of trans ferring suppression in adoptive transfer assays. Experiments using thy mectomized animals revealed that the establishment and maintenance of tolerance occurred peripherally, independently of the thymus. Adoptive transfer experiments demonstrated that ongoing graft tolerance was me diated by suppressor cells that were antigen-restricted, radiosensitiv e, and capable of preventing allograft rejection by naive as well as s ensitized cells in vivo. Studies designed to disrupt tolerance demonst rated a remarkable durability of graft protection once established, an d give insight into the identity and mechanism of action of suppressor cells generated in this model.