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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Interleukin-4 supports interleukin-12-induced proliferation and interferon-gamma secretion in human activated lymphoblasts and T helper type 1 cells.
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Interleukin-4 supports interleukin-12-induced proliferation and interferon-gamma secretion in human activated lymphoblasts and T helper type 1 cells.

机译：白细胞介素-4支持白细胞介素12诱导的人活化淋巴母细胞和1型T辅助细胞的增殖和干扰素-γ分泌。

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摘要

Interleukin-12 (IL-12) and IL-4 are known to differentially promote T helper (Th) cell differentiation. While IL-12 induces interferon-gamma (IFN-gamma) production and maturation of Th1 cells, IL-4 is thought to antagonize IL-12 and to favour Th2 development. Here we studied the combined action of various concentrations of common gamma-chain (gamma(c)-chain) cytokines, including IL-4 and the Th1 cytokine IL-12, in human activated lymphoblasts and Th1 cells. IL-4 and IL-7 potentiated IL-12-induced proliferation at every concentration tested (1-10 ng/ml) without increasing rescue from apoptosis, indicating that proliferation was directly affected by these cytokine combinations. With regards to cytokine secretion, IL-2 together with IL-12 initiated tumour necrosis factor-alpha synthesis, enhanced IFN-gamma production, and shedding of soluble IL-2 receptor alpha as expected. Importantly, combining IL-4 with IL-12 also enhanced IFN-gamma secretion in lymphoblasts and a Th1 cell line. Investigating signal transduction in lymphoblasts induced by these cytokines, we found that not only IL-2 but also IL-4 enhances signal transducer and activator of transcription 3 (STAT3) tyrosine phosphorylation by IL-12. Tyrosine phosphorylations of janus kinase 2 (JAK-2), tyrosine kinase 2 (TYK2), extracellular signal-regulated kinase (ERK) and STAT4, STAT5 and STAT6 were not potentiated by combinations of these cytokines, suggesting specificity for increased STAT3 phosphorylation. In conclusion, two otherwise antagonizing cytokines co-operate in activated human lymphoblasts and Th1 cells, possibly via STAT3 as a converging signal. These data demonstrate that IL-4 can directly enhance human Th1 cell function independently of its known actions on antigen-presenting cells. These findings should be of importance for the design of cytokine-targeted therapies of human Th-cell-driven diseases.
机译：已知白介素12（IL-12）和IL-4差异地促进T辅助（Th）细胞分化。尽管IL-12诱导Th1细胞产生干扰素-γ（IFN-γ）和成熟，但IL-4被认为可以拮抗IL-12并有利于Th2的发育。在这里，我们研究了人类激活的淋巴母细胞和Th1细胞中各种浓度的常见伽玛链（gamma（c）-chain）细胞因子（包括IL-4和Th1细胞因子IL-12）的联合作用。在每种测试浓度（1-10 ng / ml）下，IL-4和IL-7均能增强IL-12诱导的增殖，而不会增加对细胞凋亡的挽救，表明增殖直接受到这些细胞因子组合的影响。关于细胞因子的分泌，IL-2与IL-12一起启动了肿瘤坏死因子-α的合成，增强了IFN-γ的产生，并释放了可溶性IL-2受体α。重要的是，将IL-4与IL-12结合也可增强淋巴母细胞和Th1细胞系中的IFN-γ分泌。研究由这些细胞因子诱导的淋巴母细胞中的信号转导，我们发现不仅IL-2，而且IL-4都增强了IL-12的信号转导和转录3（STAT3）酪氨酸磷酸化的活化剂。 janus激酶2（JAK-2），酪氨酸激酶2（TYK2），细胞外信号调节激酶（ERK）和STAT4，STAT5和STAT6的酪氨酸磷酸化不能通过这些细胞因子的组合来增强，表明对STAT3磷酸化增加的特异性。总之，活化的人淋巴母细胞和Th1细胞中可能有两种拮抗细胞因子协同作用，可能通过STAT3作为会聚信号。这些数据表明，IL-4可以直接增强人Th1细胞的功能，而与它对抗原呈递细胞的已知作用无关。这些发现对于设计人Th细胞驱动疾病的细胞因子靶向疗法具有重要意义。

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