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‐7 (IFN‐ γ ). IFN‐ γ ‐treated ECs bound SEB effectively and stimulated T cells to proliferate and secrete tumor necrosis factor α (TNF‐ α ) and IFN‐ γ . 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‐ α and IFN‐ γ , 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‐ α and IFN‐ γ by these antibodies in SEB‐induced T cell responses may be a useful therapeutic strategy for circumventing SEB toxicity and pathogenesis. J. Leukoc. Biol. 56: 458–463; 1994.