ACTIVATION OF NATURAL-KILLER-CELLS BY HEAT-KILLED LISTERIA-MONOCYTOGENES REQUIRES ADDITIONAL SIGNALS FROM LYMPHOID-CELLS

Regulatory and protective functions have been attributed to murine nat ural killer (NK) cells in a number of infectious diseases including li steriosis. We have developed an in vitro model to study parameters und erlying the activation of naive NK cells using heat-killed Listeria mo nocytogenes (HKL) as stimulator. Independent from expression of the ce ll surface marker NK1.1, NK cells lysed YAC-1 cells after in vitro sti mulation with HKL or HKL + Interleukin (IL)-2, but not medium or IL-2 alone. In contrast, NK cells from severely immunocompromised SCID or R AG-1(-/-) mutant mice failed to respond to HKL alone, but required exo genous IL-2. Using single-gene-disruption mutant mice, we show that NK -cell activation can be supported by either T-cell receptor (TCR)alpha beta cells, TCR gamma delta cells, MHC class I or MHC class II gene p roducts. We conclude from these data that recognition of listerial com ponents alone is insufficient for activation of naive NK cells, and th at additional costimulatory signals are necessary. These can be provid ed by various lymphoid cells and appear to be cytokines.