Staphylococcal enterotoxin B activates purified NK cells to secrete IFN-gamma but requires T lymphocytes to augment NK cytotoxicity.
Staphylococcal enterotoxin B (SEB) is known for its effects on T lymphocytes; the mechanism of this activation is well studied. Although it is anticipated that there would be effects on other cells in the milieu, the mechanisms of activation of non-T immune cells are not well understood. This report examines the effects of SEB on human NK cells. Incubation of PBMC with SEB augmented NK cytotoxicity against the NK-sensitive targets K562 and Molt-4 and induced activity against the NK-resistant targets, Mel-30 and Raji. The degree of superantigen-augmented killer (SAK) activity induced by the SEB treatment correlated with the concentration of the superantigen in the mixture. Specific neutralizing Abs for lymphokines or monokines added to cultures showed that IL-2, IFN-gamma, or IL-12 each participated in the phenomenon; addition of all Abs together blocked most, but not all, SAK activity. Highly purified T lymphocytes (but not monocytes) supported the development of SAK activity in enriched cultures of CD56+ cells. The SAK activity was blocked by specific Abs to IL-2 and IFN-gamma in cocultures of T cells and CD56+ cells. In addition, SEB induced IFN-gamma secretion from sorted CD56+ cells. These data show for the first time that superantigen directly initiated cytokine synthesis in NK cells, and that SAK activity was induced as a consequence of products secreted from activated T lymphocytes. Such a superantigen effect on NK cells would place the NK lymphocyte in a pivotal role in determining the outcome of infection or immunopathology caused by superantigen exposure.
D'Orazio
J A
JA
Department of Microbiology/Immunology, University of Miami School of Medicine, FL 33101.
Burke
G W
GW
Stein-Streilein
J
J
D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D019002:CD56 Antigen; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D009500:Neutralization Tests; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D004768:Enterotoxins; D006684:HLA-DR Antigens; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma