INDUCTION OF INTERFERON-GAMMA 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-gamma (IFN-gamma) 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-gamma-production from both resting and activated human PBL and from freshly isolated murine splenocytes. Human T and NK cells produce IFN-gamma in response to NKSF, but resting PBL require the presence of nonadherent human histocompatibility leukocyte antigens DR+ (HLA-DR+) accessory cells to respond to NKSF. The mechanism(s) by which NKSF induces IFN-gamma-production results in accumulation of IFN-gamma 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-gamma-production and to synergize with other physiological IFN-gamma-inducers, joined with the previously described ability to enhance lymphocyte cytotoxicity and proliferation, indicates that this lymphokine is a powerful immunopotentiating agent.