Selective modulation of IFN-gamma mRNA stability by IL-12/NKSF

We investigated the role of IL-12 in regulating IL-2 and IFN-gamma production in primary culture of human T cells. Addition of neutralizing antiserum against the 40-kDa subunit of IL-12 to PHA-stimulated PBMC markedly reduced both IFN-gamma protein production and mRNA accumulation and stability. Moreover, concurrent treatment of partially purified T cells (> 90% CD3+) with PHA and rIL-12 selectively enhanced IFN-gamma mRNA stability and protein production, while IL-2 protein and mRNA levels were unaffected. These studies also show that IFN-gamma and IL-2 mRNA stability are temporally dissociated during the course of T cell activation, and we propose that this dissociation may be mediated through the production of IL-12. The effect of IL-12 on modulation of IFN-gamma mRNA turnover is not associated with detectable changes in either the levels or affinity of cytoplasmic RNA-binding proteins capable of recognizing AU-rich sequences in the 3'UTR of IFN-gamma mRNA.