IL-4 enhances IL-10 gene expression in murine Th2 cells in the absence of TCR engagement

Both IL-4 and IL-10 are regulatory cytokines produced by Th2 cells that can down-regulate cell-mediated immune responses. The studies reported here ex amine the influence of various cytokines in the regulation of T cell IL-10 production. The results indicate that IL-10 gene expression by TCR transgen ic Th2 cells is significantly up-regulated by IL-4 in the absence of TCR si gnals, IL-4 enhances both IL-10 mRNA levels and secreted protein, and this effect is not related to enhanced mRNA stability. TCR-mediated IL-10 gene e xpression is inhibited by cyclosporin A, but IL-4-mediated IL-10 expression is not, IL-4 also enhances IL-13 mRNA levels, to a lesser extent than IL-1 0, but does not significantly effect the expression of other cytokine mRNAs , Furthermore, IL-4 does not significantly enhance IL-10 expression in Th1 cells, IL-2 also enhances effector cytokine production in the absence of TC R signals, but in a subset nonspecific manner, increasing both Th2 IL-4 mRN A and Th1 IFN-gamma mRNA, These data suggest that Th2 IL-4 production may c ontribute to the down-regulation of immune responses by directly enhancing Th2 IL-10 production. In addition, the data clearly demonstrate that exogen ous cytokines can significantly influence effector cytokine production by e ffector T cells without the requirement for TCR signals.