Induction of Interferon y Production by Natural Killer Cell Stimulatory Factor : Characterization of the Responder Cells and Synergy with Other Inducers

We previously reported that natural killer cell stimulatory factor (NKSF), a heterodimeric lymphokine purified from the conditioned medium of human B lymphoblastoid cell lines, induces interferon y (IFN-y) production from resting peripheral blood lymphocytes (PBL) and synergizes with interleukin 2 in this activity. In this study, we show that human NKSF induces IFN-y production from both resting and activated human PBL and from freshly isolated murine splenocytes . Human T and NK cells produce IFN-,y in response to NKSF, but resting PBL require the presence of nonadherent human histocompatibility leukocyte antigens DR' (HLADR+) accessory cells to respond to NKSF. The mechanism(s) by which NKSF induces IFN-y production results in accumulation of IFN-y mRNA, is insensitive to cyclosporin A, and synergizes with those mediated by phytohemmagglutinin, phorbol diesters, anti-CD3 antibodies, and allogeneic antigens, but not by Ca2+ ionophores. The ability of NKSF to directly induce IFN-,y production and to synergize with other physiological IFN,y inducers, joined with the previously described ability to enhance lymphocyte cytotoxicity and proliferation, indicates that this lymphokine is a powerful immunopotentiating agent .