DIFFERENTIAL MODULATION OF LAK AND ADCC FUNCTIONS OF NATURAL-KILLER-CELLS FROM AK-5 TUMOR-BEARING RATS BY IL-2, IL-12 AND IFN-GAMMA

Modulation of NK cell activity by various lymphokines is well document ed. Freshly isolated NK cells exhibit natural cytotoxicity (NC) and an tibody-dependent cellular cytotoxicity (ADCC) against certain targets. Upon stimulation with IL-2, the NK cells acquire lymphokine-activated killer (LAK) activity, which enables them to kill a wide variety of t argets. Our results demonstrate that freshly isolated NH cells from tu mor-bearing rats exhibit NH activity towards YAC-1, and ADCC activity towards AH-5 targets. fresh NH cells did not lyse AH-5 targets in the absence of anti AH-5 antibody. However, in vitro culture of fresh NK c ells in the presence of rat recombinant IL-2 (r-IL-2) over a period of 7 days resulted in complete loss of ADCC activity with concomitant ac quisition of LAH activity on AK-5 tumor targets. The LAH and ADCC acti vities could be effectively distinguished based on our observation tha t monoclonal anti-rat ICAM-1 and anti-rat LFA-1 antibodies inhibited o nly LAK activity, but not ADCC activity, in addition, anti-AK-5 antise rum, but not purified anti-AK-5 antibody, inhibited LAK activity, sugg esting that soluble ICAM-1 present in hyperimmune serum could be respo nsible for inhibition of LAK activity. The loss of ADCC activity upon culture of NK cells with rIL-2 was not observed when the cultures were grown on a macrophage feeder layer. In addition, NK cells retained th eir ADCC activity when cultures were supplemented with a combination o f recombinant IL-2 and IL-12. However IL-2, IFN-gamma or IL-12 alone d id not prevent the loss of ADCC activity, suggesting the requirement o f a combination of these lymphokines for the maintainance of ADCC acti vity.