INTERFERON-GAMMA-INDUCING FACTOR ELICITS ANTITUMOR IMMUNITY IN ASSOCIATION WITH INTERFERON-GAMMA PRODUCTION

Interferon-gamma-inducing factor (IGIF) is a novel cytokine that stimu lates T-cell proliferation, augments natural killer (NK) cell lytic ac tivity, and induces interferon-gamma (IFN-gamma) production in establi shed type 1 T-helper (Th1) cells in the presence of anti-CD3 antibody. The in vitro induction of IFN-gamma by recombinant murine IGIF in the se cells was more potent than that induced by murine interleukin-12 (I L-12) and occurred apparently independent of murine IL-12. Here we rep ort that subcutaneous injection into mice of tumor cells transfected w ith murine IGIF complementary DNA (cDNA) resulted in greater than or e qual to 10-fold increase of mitogen-stimulated IFN-gamma production in cultured splenocytes. Ln addition, IGIF-transfected Renca and K1735 t umor cells can be rejected in vivo. The IGIF antitumor effect was abro gated in mice that were sublethally irradiated or depleted of both CD4 (+) and CD8(+) T cells but not in mice depleted of either subpopulatio n alone. The antitumor effect mediated by IGIF appears to be dependent on IFN-gamma production, because in vivo neutralization of IFN-gamma was accompanied by growth of IGIF-transfected tumors in 100% of the an imals. Taken together, our results show that murine IGIF can elicit T- cell-dependent antitumor immunity associated with IFN-gamma induction.