Human alveolar macrophages augment natural killer cell stimulatory factor (interleukin-12)-inducible killer activity...

Interleukin-12 (IL-12), also known as natural killer cell stimulatory factor (NKSF), was found to induce cytotoxic activity from human blood T cells and NK cells. The present study was undertaken to examine the effect of human alveolar macrophages (AM) on induction by IL-12 cytotoxic cells from blood lymphocytes. AM were obtained by bronchoalveolar lavage from healthy donors. Highly purified lymphocytes (> 99%) and monocytes (> 90%) were also isolated by centrifugal elutriation from peripheral blood of the same donors. Cytotoxicity of lymphocytes was measured by 4-h 51Cr release assay. IL-12 stimulated blood lymphocytes to produce interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), and this effect was augmented by co-cultivation with monocytes or AM. AM-upregulated induction of cytotoxic lymphocytes was stimulated with IL-12, and this effect was significantly abrogated by addition of antibodies against IFN gamma and TNF alpha. Induction by IL-12 of IFN gamma production and cytotoxic activity of CD8+ cells was also augmented by co-cultivation with monocytes or AM. AM were more effective than monocytes in augmenting the cytotoxic activity of IL-12-stimulated lymphocytes and CD8+ cells. These observations suggest that in situ induction of IL-12-stimulated cytotoxic cells in the lung may be regulated by complex cytokine networks, depending on participation of monocytes and alveolar macrophages.