Peripheral tolerance to class I mismatched renal allografts in miniature swine: Donor antigen-activated peripheral blood lymphocytes from tolerant swine inhibit antidonor CTL reactivity

Studies utilizing partially inbred miniature swine have demonstrated that a short course of cyclosporin A leads to indefinite survival of two haplotyp e class I mismatched renal allografts. Tn the present study, we have examin ed peripheral regulatory mechanisms that may be involved in maintenance of tolerance by coculturing PBT, from long-term tolerant animals with naive re cipient-matched PBL in cell-mediated lympholysis assays. We show that PBT, from tolerant animals, primed in vitro with donor Ag, suppress antidonor CT L reactivity by naive recipient-matched PBL. Suppression was not observed w hen PBT, from naive animals, primed with donor-matched PBL, were cocultured with PBL from a second naive animal, nor did PBL from either tolerant or n aive recipient-matched control animals, primed with third-party Ag, suppres s the generation of anti-third-party CTL, by a second naive animal. The sup pression was cell dose-dependent, radiation-sensitive, required cell-to-cel l contact not reversed by the provision of exogenous IL-2, and associated w ith lower levels of IL-2R expression on the suppressive effector group (par ticularly the CD8 single positive cells) when compared with the control eff ector group. These data indicate an association between the presence of per ipheral regulatory cells demonstrable in vitro and the maintenance of toler ance to renal allografts.