Role of interferons in natural killer cell generation from primitive bone marrow precursors

We studied the possible role of interferons (IFNs) on the interleukin-2 (IL-2)-dependent development of mouse natural killer (NK) cells from undifferentiated bone marrow (BM) precursors. Results indicate that alpha-IFN is able to synergize with IL-2 in the induction of lytic effectors. The stimulating effect of alpha-IFN is dose-dependent and is also obtained when BM cells are pretreated shortly before culturing. The precursor cells are resistant to treatment with 5-fluorouracil (FU, 150 mg/kg i.v.). Treatments which have been shown to eliminate more differentiated cells but spare less differentiated BM precursors, are asialoGM1-, Thy1+, Lyt1- and Lyt2-. Effector cells generated by culturing with IL-2 and alpha-IFN are typical NK cells in that they lyse only NK-susceptible targets. These are Thy1+, asialoGM1+, Lyt5+, Lyt1- and Lyt2-. These data suggest that alpha-IFN may represent a maturational signal for the generation of NK cells from undifferentiated BM precursors.