Induction of allograft tolerance in rats by an HLA class-I-derived peptide and cyclosporine A.
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.
Nisco
S
S
Department of Cardiothoracic Surgery, Stanford University, CA 94305.
Vriens
P
P
Hoyt
G
G
Lyu
S C
SC
Farfan
F
F
Pouletty
P
P
Krensky
A M
AM
Clayberger
C
C
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
D015793:HLA-B7 Antigen; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D016572:Cyclosporine