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.