IL-18 bridges innate and adaptive immunity through IFN-gamma and the CD134 pathway.
IL-18 bridges innate and adaptive immunity through IFN-gamma and the CD134 pathway.
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发表时间：
2006
影响因子：
4.4
通讯作者：
J. Maxwell;Rajwardhan Yadav;R. Rossi;Carl E. Ruby;A. Weinberg;H. Aguila;A. Vella
中科院分区：
文献类型：
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作者：
J. Maxwell;Rajwardhan Yadav;R. Rossi;Carl E. Ruby;A. Weinberg;H. Aguila;A. Vella
IL-18 诱导炎症，从而增强对病原体的保护或加剧自身免疫，并且 T 细胞在这些反应过程中被深度激活。 IL-18 如何影响 T 细胞激活尚不清楚，但这项小鼠研究表明，IL-18 促进了效应 T 细胞的 Ag 特异性 T 细胞克隆扩增，并诱导了超产 IFN-γ 的 T 细胞亚群。通过 IL-18 产生 IFN-γ 的过程独立于 NK 细胞和 IL-12，但依赖于宿主来源的 IFN-γ。为了确定这些效应器的扩增是如何发生的，IL-18 被证明可以诱导树突状细胞上的 OX40L，而肽刺激则可以诱导特定 T 细胞上的 CD134 (OX40)。 CD134 阻断可抑制 T 细胞效应器扩增，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性和适应性臂，从而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.