title: Expression of granzyme A and perforin in mouse heart transplants immunosuppressed with donor-specific transfusion and anti-CD4 monoclonal antibody.
abstract: Granzyme A and perforin are produced by activated cytotoxic T lymphocytes and their expression correlates with the appearance of cytotoxicity. Using in situ hybridization and immunohistochemistry, we examined the phenotype of cellular infiltration and the appearance of granzyme A+ and perforin+ cells in a mouse cardiac transplant model where the recipients were pretreated with donor-specific transfusion, anti-CD4 monoclonal antibody, or both. While the profiles of cellular infiltration failed to correlate with graft survival, tolerized grafts, as compared with untreated allografts, showed a decreased frequency of granzyme A and perforin expression. These functional markers of cytotoxic T lymphocytes can differentiate between rejecting and indefinitely surviving grafts and may be of value in dissecting the immunological events involved in tolerance induction.
authors.affiliation: Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, United Kingdom.
authors.forename: R H
authors.initials: RH
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Bushell
authors.forename: S V
authors.initials: SV
authors.lastname: Fuggle
authors.forename: K J
authors.initials: KJ
authors.lastname: Wood
authors.forename: P J
authors.initials: PJ
authors.lastname: Morris
mesh_terms: D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001803:Blood Transfusion; D015704:CD4 Antigens / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D053804:Granzymes; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D051381:Rats; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes; D012697:Serine Endopeptidases