LYMPHOKINE-ACTIVATED KILLER-CELLS LYSE LISTERIA-INFECTED HEPATOCYTES AND PRODUCE ELEVATED QUANTITIES OF INTERFERON-GAMMA

The bulk of Listeria monocytogenes injected intravenously into mice is taken up in the liver, where hepatocytes serve as the principal site of intracellular replication. NK cells have been implicated in host de fenses to a variety of intracellular pathogens. To explore the role of NK cells in resistance to listerial infections of the liver, lymphoki ne-activated natural killer (LAK) cells were cocultured with Listeria- infected hepatocytes, The aspartate aminotransferase activity in the m edium (evidence of cytotoxicity and hepatocyte damage) was elevated si gnificantly in these cultures. Conversely, the viability of intracellu lar Listeria organisms was reduced, Increased quantities of interferon -gamma (IFN-gamma) were also detected. IFN-gamma production by LAK cel ls was modulated by interleukin (IL)-2 and IL-12, These findings sugge st that the response of LAK cells to infected hepatocytes may play a c ritical role in host defenses to Listeria organisms taken up in the li ver.