IL-4 inhibits the synthesis of IFN-gamma and induces the synthesis of IgE in human mixed lymphocyte cultures.
IL-4 inhibits the synthesis of IFN-gamma and induces the synthesis of IgE in human mixed lymphocyte cultures.
复制标题
DOI：
10.4049/jimmunol.144.2.570
复制
发表时间：
1990-01
影响因子：
4.4
通讯作者：
Donata Vercelli;H. Jabara;R. Lauener;R. Geha
中科院分区：
文献类型：
--
作者：
Donata Vercelli;H. Jabara;R. Lauener;R. Geha
T细胞衍生的淋巴因子IL-4对于诱导人淋巴细胞合成IgE至关重要。ifn - γ可拮抗IL-4诱导ige的作用。ifn - γ的分泌在MLC中被强烈触发。因此，IL-4刺激的MLC是表征IL-4和ifn - γ之间功能拮抗作用的合适模型。在这篇报道中，我们发现当将il -4添加到人原代MLC中时，il -4持续诱导IgE合成。il -4依赖性IgE的产生需要同源的T/B细胞识别，因为它被CD3和MHC II类抗体（HlA-DR） Ag抑制。一种中和的抗ifn - γ单抗显著增强了MLC对il -4依赖性IgE的合成，表明内源性ifn - γ是IgE产生的主要抑制剂。更重要的是，在MLC和Con a激活的PBMC上清液中添加rIL-4可显著抑制ifn - γ的释放。ifn - γ蛋白的减少伴随着ifn - γ mRNA转录物表达的减少。IL-4对ifn - γ的下调可能在IL-4依赖性诱导IgE合成中发挥重要作用。
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-gamma. The secretion of IFN-gamma is vigorously triggered in MLC. Thus, IL-4-stimulated MLC represent a suitable model to characterize the functional antagonism between IL-4 and IFN-gamma. 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-gamma mAb dramatically enhanced IL-4-dependent IgE synthesis by MLC, indicating that endogenous IFN-gamma is a major inhibitor of IgE production. More importantly, addition of rIL-4 markedly inhibited the release of IFN-gamma in supernatants of MLC and Con A-activated PBMC. The decrease in IFN-gamma protein was accompanied by a decreased expression of IFN-gamma mRNA transcripts. The downregulation of IFN-gamma by IL-4 is likely to play an important role in the IL-4-dependent induction of IgE synthesis.