Influence of cytokines and immunosuppressive drugs on major histocompatibility complex class I/II expression by human cardiac myocytes in vitro.
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.
Wang
Y C
YC
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322.
Herskowitz
A
A
Gu
L B
LB
Kanter
K
K
Lattouf
O
O
Sell
K W
KW
Ahmed-Ansari
A
A
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
D000911:Antibodies, Monoclonal; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents