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The in vitro effects of human NK cells on viability of Gram-negative and Gram-positive bacteria was investigated. PBLs depleted of glass-adherent cells showed a significant antibacterial activity that was increased as the concentration of NK cells became higher. Leu-11-enriched cells exhibited the most efficient bactericidal activity. Stimulation of NK cells with staphylococcal enterotoxin B for 16 h produced a significant increase in the antibacterial activity of all NK cells tested. The antibacterial activity of monocyte-depleted cells and Leu-11-enriched cells was also enhanced after culturing in vitro for 16-24 h without exogenous cytokines. Dependence of the antibacterial activity on the presence of serum in the culture medium was not found. Ultrastructural studies revealed close contact between NK cell membranes and bacteria, no evidence of phagocytosis, and extracellular bacterial ghosts, after incubation at 37 degrees C. Supernatants from purified NK cells exhibited potent bactericidal activity with kinetics and target specificity similar to that of effector cells. These results document the potent antibacterial activity of purified NK cells and suggest an extracellular mechanism of killing.

We have recently described potent antibacterial activity of purified human NK cells. Here we show that this function is regulated by T cytotoxic/suppressor CD8+ cells. Thus, coculture of NK and CD8+ cells for 3 h or longer times abrogated the expression of the NK antibacterial activity, and of two activation markers IL-2R and transferrin receptor (Tf-R). The suppressive activity was mediated by PGE2 as demonstrated by direct PGE2 determination in CD8+ cell free supernatants, and by inhibition of CD8+ cell suppression with indomethacin or piroxicam in vitro. We also found that resting T cytotoxic/suppressor cells purified by negative selection produce higher amounts of PGE2 than adherent cells like monocytes and macrophages, and that these concentration levels are in the range of concentrations known to suppress a significant number of in vitro immunologic functions.