title: Influence of cytokines and immunosuppressive drugs on major histocompatibility complex class I/II expression by human cardiac myocytes in vitro.
abstract: Human cardiac myocytes do not express detectable levels of major histocompatibility complex (MHC) class II antigens and express low levels, if any, of MHC class I antigens. During rejection episodes, cardiac biopsies show massive increases of MHC antigens, which are thought to be induced by cytokines released by donor-sensitized recipient mononuclear cells. In efforts to determine the nature of the cytokines that induce MHC expression on cardiac myocytes, human fetal cardiac myocyte cultures were established. Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-1, IL-2, IL-3, IL-4, and tumor necrosis factor (TNF)-alpha were added to these cultures and dose/kinetics of MHC class I/II induction quantitated. Data show that IFN-gamma induces both MHC class I and II expression, and all the other cytokines (except IL-2) induce only MHC class I but not class II. Cytokines used in combination showed that IFN-alpha with TNF-alpha was the only combination that induced MHC class II expression. Addition of immunosuppressive drugs such as cytoxan, azathioprine, cyclosporine-A, and FK-506, even when added at the initiation of the cultures, did not appreciably affect the ability of the appropriate cytokines to induce MHC expression by the myocytes in vitro.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Y C
authors.initials: YC
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Herskowitz
authors.forename: L B
authors.initials: LB
authors.lastname: Gu
authors.forename: K
authors.initials: K
authors.lastname: Kanter
authors.forename: O
authors.initials: O
authors.lastname: Lattouf
authors.forename: K W
authors.initials: KW
authors.lastname: Sell
authors.forename: A
authors.initials: A
authors.lastname: Ahmed-Ansari
mesh_terms: D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005333:Fetus; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents