Regulation of IL-2 receptor subunit genes in human monocytes differential effects of IL-2 and IFN-γ

We investigated the effects of IFN-γ and IL-2 on IL-2R α and β mRNA expression in human monocytes. Low basal expression of IL-2Rβ mRNA was detected in fresh monocytes. Stimulation of monocytes with IL-2 induced a significant increase of IL-2Rβ mRNA, but did not induce IL-2Rα mRNA. In contrast, stimulation of monocytes with IFN-γ-induced IL-2Rα mRNA, but did not modify IL-2Rβ mRNA. Five U/ml of IFN-γ induced IL-2Rα mRNA and 2.2 nM of IL-2 induced IL-2Rβ mRNA, both within 3 h. Nuclear run-on experiments demonstrated that the induction of IL-2Rα mRNA by IFN-γ is controlled, at least in part, at the transcriptional level. In contrast, the enhancement of IL-2Rβ mRNA by IL-2 is controlled at a posttranscriptional level and is associated with an increase in the half-life of IL-2Rβ mRNA. The results of studies on the cytotoxic activity and on the expression of c-fms mRNA of monocytes activated by the combination of IFN-γ and IL-2 show that pretreatment with IFN-γ renders monocytes more sensitive to activation by IL-2. These results demonstrate that the IL-2Rβ and IL2Rβ subunits are induced by different lymphokines through distinct mechanisms and that both receptor subunits can influence the response of monocytes to IL-2.