Transforming growth factor-β inhibits IL-4 and IFN-γ production by stimulated human T cells
Transforming growth factor-β inhibits IL-4 and IFN-γ production by stimulated human T cells
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转化生长因子-β 抑制受刺激的人 T 细胞产生 IL-4 和 IFN-γ
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
W. Knapp
中科院分区：
文献类型：
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作者：
Wolfgang Hotter;F. Kalthoff;W. Pickl;C. Ebner;O. Majdic;D. Kraft;W. Knapp
本研究探讨了转化生长因子（TGF）-β对白血病Th 0型细胞系HUT 78、新鲜分离的人T细胞和抗原特异性人T细胞克隆产生IL-4和IFN-γ的影响。我们发现，IL-4和IFN-γ，但不是IL-2，刺激的HUT 78细胞的生产被TGF-β 1抑制。TGF-β 1还减少了IL-4和IFN-γ特异性mRNA在刺激的HUT 78细胞中的积累。然而，IL-2和IL-7共刺激IL-4和IFN-γ的产生，而IL-1、IL-3、IL-5、IL-6、IL-8、肿瘤坏死因子-α或粒细胞巨噬细胞集落刺激因子则没有作用。由于IL-2是产生IL-4和IFN-γ的重要辅助细胞因子，因此我们研究了通过IL-2受体的信号转导是否受到TGF-β 1的损害。我们发现，酪氨酸磷酸化在响应IL-2在HUT 78细胞中强烈抑制短预孵育与TGF-β 1。TGF-β 1和IL-2拮抗作用的证据来自高剂量IL-2可部分克服TGF-β 1介导的IL-4和IFN-γ产生抑制的发现。与其对HUT 78细胞的作用类似，TGF-β 1也抑制新鲜分离的T细胞以及人T细胞克隆产生IL-4和IFN-γ。总之，我们的实验表明，IL-2依赖性细胞因子IL-4和IFN-γ在IL-2产生不受部分涉及抑制IL-2/IL-2 R信号转导的机制影响的条件下均受TGF-β负控制。这些数据确定TGF-β和IL-2在调节IL-4和IFN-γ产生中为相互拮抗剂。
: The present study investigates the effect of transforming growth factor (TGF)-beta on the production of IL-4 and IFN-gamma by the leukemia Th0 type cell line HUT78, by freshly isolated human T cells, and by antigen specific human T cell clones. We found that IL-4 and IFN-gamma, but not IL-2, production by stimulated HUT78 cells was inhibited by TGF-beta 1. TGF-beta 1 also reduced the accumulation of IL-4 and IFN-gamma specific mRNA in stimulated HUT78 cells. However, IL-2 and IL-7 co-stimulated IL-4 and IFN-gamma production, whereas IL-1, IL-3, IL-5, IL-6, IL-8, tumor necrosis factor-alpha or granulocyte macrophage colony stimulating factor had no effect. Because IL-2 is an important helper cytokine for the production of IL-4 and IFN-gamma, we investigated whether signal transduction through the IL-2 receptor is impaired by TGF-beta 1. We found that tyrosine phosphorylation in response to IL-2 in HUT78 cells was strongly inhibited by a short preincubation with TGF-beta 1. Evidence for an antagonistic role for TGF-beta 1 and IL-2 comes from the finding that high doses of IL-2 could partially overcome TGF-beta 1 mediated inhibition of IL-4 and IFN-gamma production. Similar to its effect on HUT78 cells, TGF-beta 1 also inhibited IL-4 and IFN-gamma production by freshly isolated T cells as well as by human T cell clones. Taken together, our experiments show that the IL-2 dependent cytokines IL-4 and IFN-gamma are both negatively controlled by TGF-beta under conditions where IL-2 production is unaffected by a mechanism which partially involves an inhibition of IL-2/IL-2R signal transduction. These data identify TGF-beta and IL-2 as mutual antagonists in the regulation of IL-4 and IFN-gamma production.