SELECTIVE MODULATION OF IFN-GAMMA MESSENGER-RNA STABILITY BY IL-12 NKSF

We investigated the role of IL-12 in regulating IL-2 and IFN-gamma pro duction in primary culture of human T cells. Addition of neutralizing antiserum against the 40-kDa subunit of IL-12 to PHA-stimulated PBMC m arkedly reduced both IFN-gamma protein production and mRNA accumulatio n and stability. Moreover, concurrent treatment of partially purified T cells (>90% CD3(+)) with PHA and rIL-12 selectively enhanced IFN-gam ma 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 cel l activation, and we propose that this dissociation may be mediated th rough the production of IL-12. The effect of IL-12 on modulation of IF N-gamma mRNA turnover is not associated with detectable changes in eit her the levels or affinity of cytoplasmic RNA-binding proteins capable of recognizing AU-rich sequences in the 3' UTR of IFN-gamma mRNA. (C) 1994 Academic Press, Inc.