title: Induction of allograft tolerance in rats by an HLA class-I-derived peptide and cyclosporine A.
abstract: T cell recognition of MHC molecules initiates a cascade of events resulting in allograft rejection. CTLs damage the graft by targeting nonself-MHC class I molecules. We and others have previously shown that small synthetic peptides corresponding to regions of certain MHC class I molecules can inhibit the CTL response against MHC class I alloantigens in vitro. Here we report that rat heart allografts survived survived indefinitely when transplanted into recipients treated with a synthetic peptide corresponding to residues 75-84 of (B7.75-84) in combination with a subtherapeutic dose of cyclosporine A. Furthermore, this treatment induced long-term donor-specific tolerance that was mediated by anergic cells, indicating that such peptides may have potential as therapeutics for human organ transplantation.
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University, CA 94305.
authors.forename: S
authors.initials: S
authors.lastname: Nisco
authors.forename: P
authors.initials: P
authors.lastname: Vriens
authors.forename: G
authors.initials: G
authors.lastname: Hoyt
authors.forename: S C
authors.initials: SC
authors.lastname: Lyu
authors.forename: F
authors.initials: F
authors.lastname: Farfan
authors.forename: P
authors.initials: P
authors.lastname: Pouletty
authors.forename: A M
authors.initials: AM
authors.lastname: Krensky
authors.forename: C
authors.initials: C
authors.lastname: Clayberger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006085:Graft Survival / Q000187:drug effects; D015793:HLA-B7 Antigen / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007108:Immune Tolerance; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015793:HLA-B7 Antigen; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D016572:Cyclosporine