Human natural killer cytotoxic factor (NKCF): role of IFN-alpha

The relationship between production of NKCF and IFN-alpha by human lymphocytes was studied. NKCF activity was generated in response to K562-inducer cells. The presence of NKCF in supernatants was always accompanied by antiviral activity, but in several experiments IFN was detected without concomitant NKCF. In no instance was NKCF activity detected in the absence of IFN. Cell lines which were good inducers of IFN-alpha were found to be good inducers of NKCF. NKCF activity of supernatants was completely adsorbed after incubation with MOLT-4 cells, whereas there was only minimal depletion of IFN-alpha activity. Most of the antiviral activity and all of the NKCF activity of preformed supernatants was neutralized by anti-IFN-alpha serum, whereas anti-IFN-gamma serum and pH2 inactivation had minimal effect on either activity. Addition of IFN-alpha to neutralized supernatants restored NKCF activity. These experiments support the hypothesis that IFN-alpha is involved in the modulation of NKCF-lytic activity. Both antiviral and NKCF activities were abrogated when anti-IFN-alpha serum was added to cultures of lymphocytes plus inducer cells (induction phase). The addition of purified IFN-alpha to such cultures was effective in allowing resumption of NKCF activity; however, addition of IFN-gamma to these cultures did not overcome this block. The addition of purified IFN-alpha directly to supernatants generated in the presence of anti-IFN-alpha serum could not restore their NKCF activity, thereby suggesting an additional requirement for IFN-alpha in the production of NKCF. The possible role of IFN-alpha in the generation of NKCF and expression of its lytic activity is discussed.