T cells made deficient in interleukin-2 production by exposure to staphylococcal enterotoxin B in vivo are primed for interferon-gamma and interleukin-10 secretion.
The superantigen staphylococcal enterotoxin B (SEB) induces a defect in interleukin (IL)-2 production by T cells expressing specific T cell receptor V beta domains. The present study was undertaken to determine the capacity of T cells, made deficient in IL-2 production by exposure to SEB in vivo, to secrete interferon (IFN)-gamma and IL-10 and to induce pathology upon SEB rechallenge. For this purpose, BALB/c mice received two intraperitoneal injections of 100 micrograms SEB with a 48-h interval. First, we compared peak serum levels of IL-2, IFN-gamma and IL-10 after SEB rechallenge with those measured after a single SEB injection in control mice. The expected defect in IL-2 production in SEB-pretreated mice was associated with a major increase in IL-10 and IFN-gamma levels which were about fivefold higher than in controls. Experiments in mice depleted of CD4+ or CD8+ cells as well as studies in which purified T cell populations were rechallenged with SEB in vitro indicated that both CD4+ and CD8+ cells from SEB-pretreated mice were primed for IL-10 and IFN-gamma production. Furthermore, SEB-pretreated mice were sensitized to the toxic effects of the superantigen as indicated by a 30-70% lethality rate (vs. 0% in naive mice) within 48 h after SEB rechallenge. IFN-gamma was involved in the lethal syndrome as it could be prevented by injection of neutralizing anti-IFN-gamma monoclonal antibody. We conclude that SEB-reactive T cells made deficient for the production of IL-2 by exposure to SEB in vivo are primed for IFN-gamma and IL-10 production, and that IFN-gamma up-regulation is involved in the shock syndrome occurring upon SEB rechallenge.
Florquin
S
S
Laboratoire Pluridisciplinaire de Recherche Expérimentale Biomédicale, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Amraoui
Z
Z
Goldman
M
M
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology* / Q000633:toxicity; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D007376:Interleukin-2 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013047:Specific Pathogen-Free Organisms; D018089:Superantigens / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism
D004768:Enterotoxins; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma