title: Induction of tumor necrosis factor and interleukin-1 by purified staphylococcal toxic shock syndrome toxin 1 requires the presence of both monocytes and T lymphocytes.
abstract: Highly purified staphylococcal toxic shock syndrome toxin 1 (TSST-1) was tested for its ability to induce the cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) from fractionated human peripheral blood mononuclear cells prepared from seven healthy donors. Highly purified monocytes alone or T lymphocytes alone did not produce TNF or IL-1 when incubated with TSST-1 at 37 degrees C for up to 72 h. However, the addition of 10 micrograms of TSST-1 per ml to a 1:1 mixture of monocytes and T cells resulted in significant TNF (predominantly TNF-alpha) and IL-1 beta production after 24 h at 37 degrees C. The nature of the monocyte/T-cell interaction did not appear to involve gamma interferon (IFN-gamma), since 10 micrograms of rabbit anti-IFN-gamma per ml did not neutralize TNF-alpha production after TSST-1 induction. Similarly, L243, a monoclonal antibody to HLA-DR which blocks TSST-1 binding to monocytes, did not inhibit TNF-alpha production following TSST-1 induction. However, direct contact between monocytes and T cells was required, since physical separation of cells in double-chamber culture wells abolished TNF-alpha secretion after TSST-1 stimulation. Furthermore, paraformaldehyde fixation of either monocytes or T cells prior to addition to viable T cells or monocytes, respectively, also abolished TNF-alpha secretion, suggesting that aside from cell contact, soluble factors were also involved. Our results suggest that cytokine production involves more than binding of TSST-1 to its receptor on monocytes alone and that cell contact with T cells and the release of a soluble factor(s) other than IFN-gamma may be essential for the induction of cytokines by this toxin.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: R H
authors.initials: RH
authors.lastname: See
authors.forename: W W
authors.initials: WW
authors.lastname: Kum
authors.forename: A H
authors.initials: AH
authors.lastname: Chang
authors.forename: S H
authors.initials: SH
authors.lastname: Goh
authors.forename: A W
authors.initials: AW
authors.lastname: Chow
mesh_terms: D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D001427:Bacterial Toxins; D002450:Cell Communication / Q000502:physiology; D003601:Cytotoxicity Tests, Immunologic; D004768:Enterotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005557:Formaldehyde / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology; D007375:Interleukin-1 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology*; D011108:Polymers / Q000494:pharmacology; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000891:Anti-Infective Agents, Local; D001427:Bacterial Toxins; D004768:Enterotoxins; D007375:Interleukin-1; D011108:Polymers; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D005557:Formaldehyde; D007371:Interferon-gamma; C003043:paraform