STAPHYLOCOCCAL-ENTEROTOXIN-B PRIMES CYTOKINE SECRETION AND LYTIC ACTIVITY IN RESPONSE TO NATIVE BACTERIAL-ANTIGENS

Superantigens stimulate T-lymphocyte proliferation and cytokine produc tion, but the effects of superantigen exposure on cell function within a complex, highly regulated immune response remain to be determined. In this study, we demonstrate that superantigen exposure significantly alters the murine host response to bacterial antigens in an in vitro coculture system. Two days after exposure to the superantigen staphylo coccal enterotoxin B, splenocytes cultured with Streptococcus mutans p roduced significantly greater amounts of gamma interferon (IFN-gamma) and interleukin-12 than did sham-injected controls. The majority of IF N-gamma production appeared to be CD8(+) T-cell derived since depletio n of this cell type dramatically reduced the levels of IFN-gamma. To s tudy host cell damage that may occur following superantigen exposure, we analyzed cytotoxicity to ''bystander'' fibroblast cells cultured wi th splenocytes in the presence of bacterial antigens. Prior host expos ure to staphylococcal enterotoxin B significantly enhanced fibroblast cytotoxicity in the presence of bacteria. Neutralization of IFN-gamma decreased the amount of cytotoxicity observed. However, a greater redu ction was evident when splenocyte-bacterium cocultures were separated from the bystander cell monolayer via a permeable membrane support. In creased cytotoxicity appears to be primarily dependent upon cell-cell contact. Collectively, these data indicate that overproduction of infl ammatory cytokines may alter the activity of cytotoxic immune cells. S uperantigen exposure exacerbates cytokine production and lytic cell ac tivity when immune cells encounter bacteria in vitro and comparable ac tivities could possibly occur in vivo.