HUMAN ALVEOLAR MACROPHAGES AUGMENT NATURAL-KILLER-CELL STIMULATORY FACTOR (INTERLEUKIN-12)-INDUCIBLE KILLER ACTIVITY FROM AUTOLOGOUS BLOOD-LYMPHOCYTES

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 cytot oxic cells from blood lymphocytes. AM were obtained by bronchoalveolar lavage from healthy donors. Highly purified lymphocytes (> 99%) and m onocytes (> 90%) were also isolated by centrifugal elutriation from pe ripheral blood of the same donors. Cytotoxicity of lymphocytes was mea sured by 4-h Cr-51 release assay. IL-12 stimulated blood lymphocytes t o produce interferon gamma (IFN gamma) and tumor necrosis factor alpha (ThTF alpha), and this effect was augmented by co-cultivation with mo nocytes or AM. AM-upregulated induction of cytotoxic lymphocytes was s timulated with IL-12, and this effect was significantly abrogated by a ddition 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 e ffective than monocytes in augmenting the cytotoxic activity of IL-12- stimulated lymphocytes and CD8(+) cells. These observations suggest th at in situ induction of IL-12-stimulated cytotoxic cells in the lung m ay be regulated by complex cytokine networks, depending on participati on of monocytes and alveolar macrophages.