Monoclonal antibodies against mouse γ-interferon inhibit tumoricidal macrophage activation by T lymphocytes¹

A monoclonal antibody, AN-18.17.24, specific for murine interferon-gamma (IFN-γ) was produced by immunizing Wistar rats with IFN-γ secreted by a T-cell lymphoma, L12-R4, upon stimulation with phorbol myristic acetate (PMA). Antiviral activity as well as tumoricidal activation induced by PMA-stimulated L12-R4 cell supernatant or by Con A-stimulated normal spleen cells were neutralized at the same extent by AN-18 monoclonal antibody. Moreover, depletion experiments showed that inhibition of tumoricidal macrophage activation must be ascribed to the direct binding of the IFN-γ molecule by AN-18 MAb and not to the interference of the monoclonal antibody with the cell surface IFN-γ receptor. These studies conclusively demonstrate that in supematants of T lymphocytes stimulated with polyclonal activators IFN-γ was the only molecule responsible for macrophage activation in tumor cell killing.