Modulation of interferon-induced NK cells by interleukin 2 and cAMP

The mechanism by which interferon (IFN) and interleukin 2 (IL-2) activate NK cells has been examined. Added alone, either lymphokine activates NK cells; together they synergize. NK cells generated by IFN, IL-2 or IFN plus IL-2 are indistinguishable on the basis of their cell surface phenotype. Precursor NK cells are Qa5+, MK 2.2-, Ly-6- and effector NK cells are Qa5+, MK 2.2+, Ly-6+. Sequential factor addition showed that IFN must be present at the start of culture, whereas IL-2 could be added later with no loss of effect. Antibody to IFN was shown to block not only the action of IFN but also to prevent NK cell activation by IL-2. These results are taken to suggest that IFN initiates NK cell activation and IL-2 controls later stages. The synergistic effect of IL-2 is counteracted by cAMP. Considering the variety of systems in which IL-2 is active and the diversity of its effects, it is proposed that its antagonism with cAMP may be a basis for the biologic activity of IL-2.