Costimulatory receptors for the superantigen staphylococcal enterotoxin B on human vascular endothelial cells and T cells.
Cell-surface molecules on human vascular endothelial cells (ECs) and T lymphocytes that mediate staphylococcal enterotoxin B (SEB)-induced T cell proliferation and cytokine production were investigated. Expression of HLA-DR and intercellular adhesion molecule 1 (ICAM-1) on EC was induced by interferon-gamma (IFN-gamma). IFN-gamma-treated ECs bound SEB effectively and stimulated T cells to proliferate and secrete tumor necrosis factor alpha (TNF-alpha) and IFN-gamma. SEB-induced T cell proliferation was inhibited by monoclonal antibodies to CD2, CD11a, CD28, ICAM-1, and endothelial leukocyte adhesion molecule (ELAM). These antibodies also blocked production of the proinflammatory mediators, TNF-alpha and IFN-gamma, in SEB-stimulated T cell-EC cocultures. These results suggest that the surface molecules, CD11a:CD18/ICAM-1, CD2, CD28, and ELAM, are all important costimulatory receptors for T cell activation by superantigens with the EC as the antigen-presenting cell. Thus, like conventional antigens, multiple stimulatory signals from the interactions of these receptors are required for superantigen-induced immune responses with ECs and T cells. Reducing proinflammatory mediators such as TNF-alpha and IFN-gamma by these antibodies in SEB-induced T cell responses may be useful therapeutic strategy for circumventing SEB toxicity and pathogenesis.
Krakauer
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Applied Research Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011.
D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D004730:Endothelium, Vascular / Q000502:physiology*; D004768:Enterotoxins / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D004768:Enterotoxins; D006684:HLA-DR Antigens; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma