GITRL on inflammatory antigen presenting cells in the lung parenchyma provides signal 4 for T-cell accumulation and tissue-resident memory T-cell formation.,Mucosal Immunology

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GITRL on inflammatory antigen presenting cells in the lung parenchyma provides signal 4 for T-cell accumulation and tissue-resident memory T-cell formation.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-Nov-28 , DOI: 10.1038/s41385-018-0105-5
Kuan-Lun Chu ₁ , Nathalia V Batista ₁ , Kuan Chung Wang ₁ , Angela C Zhou ₁ , Tania H Watts ₁

Affiliation

T-cell responses in the lung are critical for protection against respiratory pathogens. TNFR superfamily members play important roles in providing survival signals to T cells during respiratory infections. However, whether these signals take place mainly during priming in the secondary lymphoid organs and/or in the peripheral tissues remains unknown. Here we show that under conditions of competition, GITR provides a T-cell intrinsic advantage to both CD4 and CD8 effector T cells in the lung tissue, as well as for the formation of CD4 and CD8 tissue-resident memory T cells during respiratory influenza infection in mice. In contrast, under non-competitive conditions, GITR has a preferential effect on CD8 over CD4 T cells. The nucleoprotein-specific CD8 T-cell response partially compensated for GITR deficiency by expansion of higher affinity T cells; whereas, the polymerase-specific response was less flexible and more GITR dependent. Following influenza infection, GITR is expressed on lung T cells and GITRL is preferentially expressed on lung monocyte-derived inflammatory antigen presenting cells. Accordingly, we show that GITR+/+ T cells in the lung parenchyma express more phosphorylated-ribosomal protein S6 than their GITR-/- counterparts. Thus, GITR signaling within the lung tissue critically regulates effector and tissue-resident memory T-cell accumulation.

中文翻译：

肺实质中炎症抗原呈递细胞上的 GITRL 为 T 细胞积累和组织驻留记忆 T 细胞形成提供信号 4。

肺中的 T 细胞反应对于抵御呼吸道病原体至关重要。TNFR 超家族成员在呼吸道感染期间为 T 细胞提供生存信号方面发挥着重要作用。然而，这些信号是否主要发生在次级淋巴器官和/或外周组织的启动过程中仍然未知。在这里，我们表明在竞争条件下，GITR 为肺组织中的 CD4 和 CD8 效应 T 细胞以及呼吸道流感感染期间 CD4 和 CD8 组织驻留记忆 T 细胞的形成提供了 T 细胞内在优势在小鼠中。相反，在非竞争性条件下，GITR 对 CD8+ T 细胞的作用优先于 CD4+ T 细胞。核蛋白特异性 CD8 T 细胞反应通过扩增更高亲和力的 T 细胞来部分补偿 GITR 缺陷；然而，聚合酶特异性反应的灵活性较低且更依赖于 GITR。流感感染后，GITR 在肺 T 细胞上表达，GITRL 优先在肺单核细胞衍生的炎性抗原呈递细胞上表达。因此，我们表明肺实质中的 GITR+/+ T 细胞比它们的 GITR-/- 对应物表达更多的磷酸化核糖体蛋白 S6。因此，肺组织内的 GITR 信号传导严格调节效应器和组织驻留记忆 T 细胞的积累。我们显示肺实质中的 GITR+/+ T 细胞比它们的 GITR-/- 对应物表达更多的磷酸化核糖体蛋白 S6。因此，肺组织内的 GITR 信号传导严格调节效应器和组织驻留记忆 T 细胞的积累。我们显示肺实质中的 GITR+/+ T 细胞比它们的 GITR-/- 对应物表达更多的磷酸化核糖体蛋白 S6。因此，肺组织内的 GITR 信号传导严格调节效应器和组织驻留记忆 T 细胞的积累。

更新日期：2019-01-26

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