IL-4 inhibits the synthesis of IFN-γ and induces the synthesis of IgE in human mixed lymphocyte cultures

The T cell-derived lymphokine IL-4 is essential for the induction of IgE synthesis by human lymphocytes. The IgE-inducing effect of IL-4 is antagonized by IFN-γ. The secretion of IFN-γ is vigorously triggered in MLC. Thus, IL-4-stimulated MLC represent a suitable model to characterize the functional antagonism between IL-4 and IFN-γ. In this report, we show that rIL-4 consistently induced IgE synthesis when added to human primary MLC. IL-4-dependent IgE production required cognate T/B cell recognition, because it was inhibited by antibodies to CD3 and MHC class II (HLA-DR) Ag. A neutralizing anti-IFN-γ mAb dramatically enhanced IL-4-dependent IgE synthesis by MLC, indicating that endogenous IFN-γ is a major inhibitor of IgE production. More importantly, addition of rIL-4 markedly inhibited the release of IFN-γ in supernatants of MLC and Con A-activated PBMC. The decrease in IFN-γ protein was accompanied by a decreased expression of IFN-γ mRNA transcripts. The downregulation of IFN-γ by IL-4 is likely to play an important role in the IL-4-dependent induction of IgE synthesis.