Human Alveolar Macrophages Augment Natural Killer Cell Stimulatory Factor (Interleukin-12)-inducible Killer Activity from Autologous Blood Lymphocytes

Abstract

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 γ (IFNγ) and tumor necrosis factor α (TNFα), 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 IFNγ and TNFα. Induction by IL‐12 of IFNγ 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.