title: Antigen persistence and time of T-cell tolerization determine the efficacy of tolerization protocols for prevention of skin graft rejection.
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.
authors.affiliation: Institute of Experimental Immunology, Department of Pathology, University of Zürich. stephanehl@aol.com
authors.forename: S
authors.initials: S
authors.lastname: Ehl
authors.forename: P
authors.initials: P
authors.lastname: Aichele
authors.forename: H
authors.initials: H
authors.lastname: Ramseier
authors.forename: W
authors.initials: W
authors.lastname: Barchet
authors.forename: J
authors.initials: J
authors.lastname: Hombach
authors.forename: H
authors.initials: H
authors.lastname: Pircher
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D000956:Antigens, Viral; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007108:Immune Tolerance; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014764:Viral Proteins
chemical_list: D000941:Antigens; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus