Mechanisms of IFN-gamma induction by natural killer cell stimulatory factor (NKSF/IL-12). Role of transcription and mRNA stability in the synergistic interaction between NKSF and IL-2.

We have investigated the molecular mechanisms regulating IFN-gamma production in human T lymphocytes stimulated by NK cell stimulatory factor (NKSF/IL-12). We show that NKSF synergizes with IL-2 and phorbol diesters inducing the accumulation of IFN-gamma mRNA in PHA-activated T cell blasts. NKSF regulates IFN-gamma mRNA expression in PHA blasts and the T leukemia cell line, TALL-103/2, at both the transcriptional and posttranscriptional levels. NKSF increases the transcriptional rate for IFN-gamma in both these cell types, as determined by nuclear run-on analysis. However, synergy between NKSF and IL-2 can be demonstrated only at the level of mRNA stability, and both cytokines are required to increase IFN-gamma mRNA half-life.