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 celIs 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 mu g 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 SEE 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 SEE rechallenge.