Activation of mouse liver natural killer cells and NK1.1(+) T cells by bacterial superantigen-primed Kupffer cells

Although bacterial superantigens have been well characterized as potent sti mulators of T cells, their role in natural killer (NK)-type cells remains l argely unknown. In the present study, we examined the effect of bacterial s uperantigens on mouse liver NK cells and NK1.1 Ag+ (NK1(+)) T cells. C57BL/ 6 mice were intravenously injected with staphylococcal enterotoxin B (SEB) or streptococcal pyrogenic exotoxin A (SPE-A), and mononuclear cells (MNC) of various organs were obtained from mice 4 hours after bring injected with superantigen, MNC were cultured for 48 hours, and interferon gamma (IFN-ga mma) levels of supernatants were measured. The antitumor cytotoxicities of the liver and spleen MNC were also evaluated 24 hours after the mice were i njected with superantigen. Liver MNC produced more IFN-gamma than did splen ocytes, and peripheral blood and lung MNC did not produce any detectable IF N-gamma. In addition, liver MNC acquired a potent antitumor cytotoxicity by the SEE injection, and both NK cells and NK1(+)T cells but not cluster of differentiation (CD)8(+) T cells were responsible for the cytotoxicity as d emonstrated by either in vivo or in vitro cell depletion experiments, and t he NK-type cells were partly responsible for the increased serum IFN-gamma, Activation of liver NK-type cells was also supported by the fact that live r NK cells proportionally increased and NK1(+)T cells augmented their CD11a expressions after SEE injection. The pretreatment of mice with anti-IFN-ga mma Ab and/or with anti-interleukin-12 (IL-12) Ab diminished the SEE-induce d cytotoxicity of liver MNC, Furthermore, the in vivo depletion of Kupffer cells decreased the SEE-induced cytotoxicity of liver MNC. Consistent with these results, liver MNC stimulated with superantigens in the presence of K upffer cells in vitro produced a greater amount of IFN-gamma than did the l iver MNC without Kupffer cells or splenocytes. Our results suggest that bac terial superantigen-primed Kupffer cells produce IL-12 and other monokines, while also nonspecifically activating both NK cells and NK1(+) T cells to produce IFN-gamma.