Cell adhesion molecules are co-receptors for staphylococcal enterotoxin B-induced T-cell activation and cytokine production.
Enterotoxins produced by Staphylococcus aureus are potent mitogens for human T cells and cause lethal toxic shock. These superantigens bind to major histocompatibility complex class II on antigen-presenting cells outside the conventional peptide-binding groove and stimulate T cells expressing certain T-cell receptor V beta gene products. We investigated other cell-surface molecules on human peripheral blood mononuclear cells that can mediate staphylococcal enterotoxin B (SEB)-induced T-cell proliferation and cytokine production. SEB-induced proliferation of T cells was inhibited by monoclonal antibodies to CD2, CD11a, CD18, CD28, CD44, CD58 and ICAM-1. Anti-ICAM-1 also blocked the production of pro-inflammatory mediators, TNF alpha and IFN gamma by SEB-stimulated T cells. These data suggest that the surface molecules, CD11a:CD18/ICAM-1, CD2/CD58, CD28 and CD44, are all important co-receptors for T-cell activation by superantigens. Thus, like conventional antigens, multiple stimulatory signals from the interactions of these receptors are required for superantigen-induced immune responses. Reducing toxic mediators such as TNF alpha and IFN gamma by anti-ICAM antibodies in SEB-induced T-cell responses may be a useful therapeutic strategy to circumvent SEB toxicity and pathogenesis.
Applied Research Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011.
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Krakauer
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004768:Enterotoxins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016023:Integrins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004768:Enterotoxins; D016023:Integrins; D018089:Superantigens; C031818:enterotoxin B, staphylococcal