The mechanism of enhancement of natural killer cell activity by soluble streptococcal products.
Products prepared from broth extracts of beta-hemolytic Group A streptococci activate human natural killer (NK) cells. The active moiety is likely a protein since the enhancing capability is destroyed by the proteolytic enzyme pronase, although not by trypsin. The enhancement in NK cytotoxicity is due at least in part to lymphokines, since normal peripheral blood mononuclear cells and T cells, upon incubation with streptococcal products (SP), release supernatant factors which augment NK activity. These cell culture supernatants contain interferons (IFN) as well as low levels of interleukin-2 (IL-2). Treatment of supernatants with anti-IFN antibodies has variable effects, depending on the donor cells used to produce the factors. In most cases, anti-IFN-gamma totally abrogates enhancement. Treatment of supernatants with antibodies to IFN-alpha modestly decreases enhancement of most donor cells; however, IFN-alpha appears not to be a major factor in SP-activated lymphokines. Pretreating effector cells with a monoclonal antibody directed against the IL-2 receptor (anti-Tac) usually reduces the supernatant effect. The combination of anti-Tac and anti-IFN-gamma totally nullifies enhancement. Thus T lymphocytes stimulated with streptococcal products augment NK activity at least in part by producing IFN-gamma and a factor whose activity is reduced by the interaction of the IL-2 receptor with anti-Tac.
D000906:Antibodies / Q000276:immunology; D002469:Cell Separation; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007372:Interferons / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000032:analysis / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000906:Antibodies; D008222:Lymphokines; D007372:Interferons