Direct activation of murine T cells by staphylococcal enterotoxins.
The capacity of staphylococcal enterotoxins to stimulate all T cells bearing certain TCR variable region alleles has generated a great deal of interest. This stimulation appears to involve specific binding of the toxin to class II molecules and subsequent stimulation of the T cell via the TCR V beta elements. Recent studies from our laboratory have focused on the ability of staphylococcal enterotoxins to directly activate purified lymph node T cells and a panel of T cell clones and hybridomas. A T cell costimulation assay was performed to assess cellular activation requirements and cytokine receptor expression. Activation of highly purified lymph node T cells by staphylococcal enterotoxin B (SEB) required costimulatory signals which could be provided by IL-1, IL-2, IL-4, or IL-6, whereas SEB alone demonstrated no significant proliferative response. Using a panel of TH1 and TH2 cell clones and T cell hybridomas possessing various responsive and nonresponsive V beta alleles, it was possible to demonstrate that SEA and SEB costimulate T cells via the TCR complex. Additionally, enterotoxin-pretreated T cells demonstrated a significant proliferative response upon exposure to class II-bearing accessory cells, suggesting that these toxins bind directly to T cells. Highly purified T cells cultured with both SEB and IL-1 exhibit significantly increased levels of IL-2 receptor, whereas cells cultured with SEB or IL-1 alone demonstrated low levels of this receptor. These results do not exclude an association of the staphylococcal enterotoxins with class II molecules in a manner which results in a high avidity binding to the TCR required for transduction of the appropriate activation signals. In the absence of class II molecules, however, these superantigens can still bind to T cells, and the activation signal is delivered in the presence of cytokines that trigger T cell growth and lymphokine production.
Taub
D D
DD
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Rogers
T J
TJ
D000818:Animals; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D004768:Enterotoxins; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; C031818:enterotoxin B, staphylococcal