A T-cell hybridoma produced by fusion of concanavalin A-stimulated murine splenocytes produced a factor (MAFH) capable of activating tumoricidal capacity by responsive murine peritoneal macrophages. Macrophages treated with the MAFH required an additional trigger signal of bacterial lipopolysaccharide (LPS) for maximal activity. In contrast to interferon-γ (IFNγ), which induced tumoricidal activity against all tumor cells tested, MAFH only induced macrophage-mediated kill of the BI6P51 and 168 lines, and not of the P815 or B16BL6 lines. An identical pattern of tumoricidal activity was obtained by treating macrophages with recombinant interleukin-4 (IL-4). The active moiety of MAFH appeared to be IL-4 as (i) monoclonal antibody against IL-4 blocked MAFH, but not IFNγ, activity, and (ii) the T-cell hybridoma contained large amounts of mRNA for IL-4 and no detectable mRNA for IFNγ (as determined by Northern dot analysis). The pattern of tumoricidal activity observed may be due to an IL-4 mediated enhancement of tumor necrosis factor production by LPS-triggered macrophages.
ASJC Scopus subject areas
- Cell Biology