Interferon (IFN) augments the cytotoxic function of natural killer (NK) and killer (K) cells. We have previously shown that all NK- and K-cell function resides in the HNK-1+ population of granular lymphocytes. The present experiments demonstrated that IFN significantly augmented the efficiency of purified HNK-1+ cells to perform both NK- and K-cell function. In contrast, HNK-1- cells could not lyse target cells even in the presence of IFN. IFN did not generate new HNK-1+ cells from the pool of HNK-1- cells. We then examined the possibility that IFN might induce the maturation of immature NK cells previously defined as having an HNK+T3+ phenotype and a paucity of cytoplasmic granules. However, no changes were observed either in the proportion of HNK-1+ cells expressing the T3 antigen or in the number of granules within each HNK-1+ cell even after an 18-hr incubation with IFN. While fresh HNK-1- cells lack NK-cell function, they can acquire NK-like activity without expressing the HNK-1 antigen after incubation with either alloantigens or mitogens. When incubated further with IFN, these alloantigen- or PHA-activated HNK-1- cells with NK-like activity demonstrated relatively little augmentation of their cytotoxicity. It is concluded that interferon exerts its influence on restricted subpopulations of cells, primarily HNK-1+ cells. Its mechanism appears to concern the cytotoxic event rather than influencing cellular maturation.
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