IL-18 bridges innate and adaptive immunity through IFN-γ and the CD134 pathway
IL-18 bridges innate and adaptive immunity through IFN-γ and the CD134 pathway
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DOI：
10.4049/jimmunol.177.1.234
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Vella, Anthony T.
中科院分区：
文献类型：
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作者：
Maxwell, Joseph R.;Yadav, Rajwardhan;Vella, Anthony T.
IL-18诱导炎症，导致对病原体的保护增强或自身免疫加剧，T细胞在这些反应中被深刻激活。IL-18如何影响T细胞活化尚不清楚，但这项小鼠研究表明，IL-18促进了ag特异性T细胞克隆扩增效应T细胞，并诱导了ifn - γ超产T细胞亚群。通过IL-18产生ifn - γ的承诺独立于NK细胞和IL-12，但依赖于宿主来源的ifn - γ。为了确定这些效应物是如何扩增的，IL-18在树突状细胞上诱导OX40L，而肽刺激在特异性T细胞上诱导CD134 （OX40）。CD134阻断抑制T细胞效应扩增，从而使ifn - γ超级生产者的数量减少12倍。因此，独立于IL-12， IL-18通过ifn - γ和CD134共刺激途径桥接免疫系统的先天和适应性臂，影响整个淋巴和非淋巴组织的T细胞免疫。
IL-18 induces inflammation resulting in either enhanced protection from pathogens or exacerbation of autoimmunity, and T cells are profoundly activated during these responses. How IL-18 influences T cell activation is unknown, but this study in mice shows that IL-18 boosted Ag-specific T cell clonal expansion of effector T cells and induced a subpopulation of IFN-gamma superproducing T cells. Commitment to IFN-gamma production through IL-18 was independent of NK cells and IL-12 but dependent on host-derived IFN-gamma. To determine how expansion of these effectors occurred, IL-18 was shown to induce OX40L on dendritic cells, whereas peptide stimulation induced CD134 (OX40) on specific T cells. CD134 blockade inhibited T cell effector expansion thereby reducing the number of IFN-gamma superproducers by 12-fold. Thus, independent of IL-12, IL-18 impacts T cell immunity throughout lymphoid and nonlymphoid tissue by bridging the innate and adaptive arms of the immune system through IFN-gamma and the CD134 costimulatory pathway.