Antigen persistence and time of T-cell tolerization determine the efficacy of tolerization protocols for prevention of skin graft rejection
Nature medicine, 1998•nature.com
We studied antigen-specific T-cell tolerization therapy using skin transplantation across a
defined minor histocompatibility antigen difference. 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 transient, and antigen presentation by
the graft was not sufficient to maintain tolerance. In contrast, transfer of antigen-expressing …
defined minor histocompatibility antigen difference. 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 transient, and antigen presentation by
the graft was not sufficient to maintain tolerance. In contrast, transfer of antigen-expressing …
Abstract
We studied antigen-specific T-cell tolerization therapy using skin transplantation across a defined minor histocompatibility antigen difference. 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 transient, and antigen presentation by the graft was not sufficient to maintain tolerance. In contrast, transfer of antigen-expressing lymphoid cells induced long-lasting tolerance correlating with donor cell chimerism. These findings show that antigen-specific tolerization can induce graft acceptance even when begun after transplantation and that long-term graft survival depends on persistence of the tolerizing antigen.
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