Indirect inhibition of generation of murine lymphokine-activated killer cell activity in splenocyte cultures by interferon-gamma

The effect of mouse recombinant interferon-gamma (rIFN-γ) on murine lymphokine-activated killer (LAK) cell activity was investigated using natural killer (NK)-resistant, spontaneously developed, weakly immunogenic and highly tumourigenic, syngeneic murine mammary adenocarcinoma, JC, mimicking that of human disease, as the target. Murine YAC-1 also was used as a target cell line. rIFN-γ, when used in combination with recombinant interleukin-2 (rIL-2), was shown to exhibit a suppressed effect on LAK cell activity generated from BALB/c mouse splenocytes, compared to that with rIL-2 alone. The decrease in LAK cell activity was rIFN-γ dose-dependent. Kinetic study revealed that this inhibitory effect was demonstrated when rIFN-γ was added to the medium at the early phase of rIL-2 culture. The inhibitory effect on LAK cell generation by rIFN-γ was completely abrogated when the nylon-wool-treated non-adherent 'macrophage-free' splenocytes were incubated with rIL-2 and rIFN-γ. These results indicated that the LAK cell activity generated from murine splenocytes cultured with rIL-2 could be depressed by rIFN-γ, and that the macrophages may be involved as mediators.