Influenza A virus-induced IFN-alpha/beta and IL-18 synergistically enhance IFN-gamma gene expression in human T cells.
Influenza A virus-induced IFN-alpha/beta and IL-18 synergistically enhance IFN-gamma gene expression in human T cells.
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发表时间：
1998-06
影响因子：
4.4
通讯作者：
T. Sareneva;S. Matikainen;M. Kurimoto;I. Julkunen
中科院分区：
文献类型：
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作者：
T. Sareneva;S. Matikainen;M. Kurimoto;I. Julkunen
T细胞在宿主对病毒和细菌感染的早期防御中起着重要作用，对清除病原体至关重要。ifn - γ是活化的T细胞和NK细胞的产物，除了具有直接的抗菌活性外，还在激活细胞介导的免疫中起主要作用。在这里，我们报告了甲型流感病毒感染的巨噬细胞分泌的细胞因子能够诱导人T细胞中ifn - γ的合成。甲型流感病毒感染的人外周巨噬细胞分泌ifn - α / β、tnf - α、il -1 β和最近发现的细胞因子IL-18（或ifn - γ诱导因子），而IL-12的产生未被检测到。从病毒感染的巨噬细胞收集的上清液诱导T细胞中ifn - γ mRNA的快速表达和蛋白的产生。这可以通过加入中和性抗ifn - α / β抗体来下调，而中和性抗il -12抗体对ifn - γ基因表达没有影响。外源性添加ifn - α / β也能快速刺激T细胞中ifn - γ mRNA的合成，而不依赖于蛋白质的合成。IL-18与ifn - α协同上调ifn - γ基因表达和蛋白生成。这些数据表明，病毒感染期间巨噬细胞产生的ifn - α / β和IL-18可能共同作用，诱导ifn - γ合成，因此，这两种细胞因子可能在th1型免疫反应的发展中发挥重要作用。
T cells contribute significantly the to host's early defense against viral and bacterial infections and are essential for clearance of the pathogen. IFN-gamma, a product of activated T and NK cells, has, in addition to its direct antimicrobial activity, a major role in activating cell-mediated immunity. Here we report that cytokines secreted by influenza A virus-infected macrophages are able to induce IFN-gamma synthesis in human T cells. Influenza A virus-infected human peripheral macrophages secreted IFN-alpha/beta, TNF-alpha, IL-1beta, and a recently identified cytokine, IL-18 (or IFN-gamma-inducing factor), whereas the production of IL-12 was not detected. Supernatants collected from virus-infected macrophages induced rapid IFN-gamma mRNA expression and protein production in T cells. This was down-regulated by the addition of neutralizing anti-IFN-alpha/beta Abs, whereas neutralizing anti-IL-12 Abs had no effect on IFN-gamma gene expression. Exogenously added IFN-alpha/beta also rapidly stimulated the synthesis of IFN-gamma mRNA in T cells independently of protein synthesis. IL-18 synergized with IFN-alpha to up-regulate IFN-gamma gene expression and protein production. The data suggest that IFN-alpha/beta and IL-18 produced by macrophages during virus infection may act together to induce IFN-gamma synthesis and, consequently, may play an important role for both of these cytokines in the development of Th1-type immune responses.