title: Temporal relationship of cytokine release by peripheral blood mononuclear cells stimulated by the streptococcal superantigen pep M5.
abstract: We undertook this study to determine the quality, quantity, and temporal relationship of pep M5-induced cytokine release. The ability of pep M5 to stimulate interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) production by a T-cell-depleted, monocyte- and B-cell-enriched cell population was dependent on the presence of T cells. The requirement for T cells could be met by addition of exogenous gamma interferon (IFN-gamma). In the presence of IFN-gamma, pep M5 induced the release of TNF-alpha, IL-1, and IL-6, TNF-alpha levels peaked at 24 h, while IL-1 and IL-6 levels peaked at 48 h. pep M5 induced T cells to produce IFN-gamma, which may have accounted for the ability of the super antigen to induce the production of IL-1, IL-6, TNF-alpha, and TNF-beta by peripheral blood mononuclear cells (PBMC). The addition of excess IFN-gamma to cultures of pep M5 and PBMC did not further increase the release of these cytokines at 24 and 48 h but resulted in sustained higher levels at 72 h. Interestingly, TNF-beta production occurred only in the presence of pep M5 and exogenous IFN-gamma. The ability of pep M5 to induce cytokine production was compared with that of a potent super antigen, staphylococcal enterotoxin B (SEB). SEB was a 2- to 14-fold-more-potent inducer of IFN-gamma production. Furthermore, the profile of cytokine released by PBMC in response to this super antigen mimicked that seen with pep M5 in the presence of exogenous IFN-gamma. In conclusion, pep M5 induces the production of cytokines that are involved in immune regulation and inflammation. These cytokines also play a major role in human T-cell responses to this super antigen.
authors.affiliation: Veterans Affairs Medical Center, Memphis, Tennessee 38104.
authors.forename: M
authors.initials: M
authors.lastname: Kotb
authors.forename: H
authors.initials: H
authors.lastname: Ohnishi
authors.forename: G
authors.initials: G
authors.lastname: Majumdar
authors.forename: S
authors.initials: S
authors.lastname: Hackett
authors.forename: A
authors.initials: A
authors.lastname: Bryant
authors.forename: G
authors.initials: G
authors.lastname: Higgins
authors.forename: D
authors.initials: D
authors.lastname: Stevens
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004768:Enterotoxins / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D016207:Cytokines; D004768:Enterotoxins; C014689:streptococcal M protein; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma