Enhancing effect of natural killer cell stimulatory factor (NKSF/interleukin‐12) on cell‐mediated cytotoxicity against tumor‐derived and virus‐infected cells

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Abstract
Natural killer cell stimulatory factor (NKSF) or interleukin‐12 (IL‐12) is a heterodimeric cytokine with pleiomorphic effects on T and NK cells, including induction of lymphokine production, mitogenesis, and enhancement of spontaneous cytotoxic activity. Similarly to IL‐2, NKSF/IL‐12 enhances NK cell‐mediated cytotoxicity within a few hours and independently from induced proliferation. This effect is independent from other induced cytokines, because it is not prevented by antibodies neutralizing interferon (IFN)‐α, IFN‐β IFN‐γ, IL‐2 or tumor necrosis factor (TNF)‐α and, unlike the induction of IFN‐γ production by peripheral blood lymphocytes, it does not require HLA class II‐positive accessory cells. Enhanced cytotoxicity is accompanied by morphologic changes in NK cells, including a significant increase in the number of cytoplasmic granules. In addition to the previously described ability to enhance the cytotoxic activity of NK cells against tumor‐derived target cells, NKSF/IL‐12 is also a potent stimulator of cytotoxicity against virus‐infected cells, either fibroblasts acutely infected with herpes viruses or T cell lines chronically infected with human immunodeficiency virus‐1. NK cell‐mediated antibody‐dependent cytotoxicity or anti‐CD16 antibody‐redirected lysis is not significantly enhanced by NKSF/IL‐12. However, the ability of resting peripheral blood T cells to mediate anti‐CD3 antibody‐redirected lysis is enhanced by 18‐h incubation with NKSF/IL‐12, indicating that this lymphokine can modulate the cytotoxic capability of both NK and T cells.

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