ANTIGEN PERSISTENCE AND TIME OF T-CELL TOLERIZATION DETERMINE THE EFFICACY OF TOLERIZATION PROTOCOLS FOR PREVENTION OF SKIN-GRAFT REJECTION

We studied antigen-specific T-cell tolerization therapy using skin tra nsplantation across a defined minor histocompatibility antigen differe nce. Specific tolerization protocols using short-lived peptide or long -lived spleen cells presenting the peptide as antigen prevented graft rejection without immunosuppression when started before or as long as 10 days after transplantation. Peptide-induced T-cell tolerance was tr ansient, and antigen presentation by the graft was not sufficient to m aintain tolerance. In contrast, transfer of antigen-expressing lymphoi d cells induced long-lasting tolerance correlating with donor cell chi merism. These findings show that antigen-specific tolerization can ind uce graft acceptance even when begun after transplantation and that lo ng-term graft survival depends on persistence of the tolerizing antige n.