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Pulmonary monocytes interact with effector T cells in the lung tissue to drive TRM differentiation following viral infection.
Mucosal Immunology ( IF 8 ) Pub Date : 2019-11-13 , DOI: 10.1038/s41385-019-0224-7
Paul R Dunbar 1 , Emily K Cartwright 1 , Alexander N Wein 1 , Tetsuo Tsukamoto 2 , Zheng-Rong Tiger Li 1 , Nivedha Kumar 1 , Ida E Uddbäck 3 , Sarah L Hayward 1 , Satoshi Ueha 4 , Shiki Takamura 2 , Jacob E Kohlmeier 1, 5
Affiliation  

Lung resident memory CD8 T cells (TRM) are critical for protection against respiratory viruses, but the cellular interactions required for their development are poorly understood. Herein we describe the necessity of classical monocytes for the establishment of lung TRM following influenza infection. We find that, during the initial appearance of lung TRM, monocytes and dendritic cells are the most numerous influenza antigen-bearing APCs in the lung. Surprisingly, depletion of DCs after initial T cell priming did not impact lung TRM development or maintenance. In contrast, a monocyte deficient pulmonary environment in CCR2-/- mice results in significantly less lung TRM following influenza infection, despite no defect in the antiviral effector response or in the peripheral memory pool. Imaging shows direct interaction of antigen-specific T cells with antigen-bearing monocytes in the lung, and pulmonary classical monocytes from the lungs of influenza infected mice are sufficient to drive differentiation of T cells in vitro. These data describe a novel role for pulmonary monocytes in mediating lung TRM development through direct interaction with T cells in the lung.

中文翻译:

肺单核细胞与肺组织中的效应 T 细胞相互作用,以在病毒感染后驱动 TRM 分化。

肺驻留记忆 CD8 T 细胞 (TRM) 对于抵御呼吸道病毒至关重要,但对其发育所需的细胞相互作用知之甚少。在此我们描述了经典单核细胞在流感感染后建立肺 TRM 的必要性。我们发现,在肺部 TRM 最初出现期间,单核细胞和树突状细胞是肺部数量最多的携带流感抗原的 APC。令人惊讶的是,初始 T 细胞启动后 DC 的耗尽不会影响肺 TRM 的发育或维持。相比之下,尽管抗病毒效应反应或外周记忆库没有缺陷,但 CCR2-/- 小鼠中单核细胞缺陷的肺部环境导致流感感染后肺部 TRM 显着减少。成像显示抗原特异性 T 细胞与肺中携带抗原的单核细胞直接相互作用,而来自流感感染小鼠肺部的肺经典单核细胞足以在体外驱动 T 细胞分化。这些数据描述了肺单核细胞通过与肺中 T 细胞直接相互作用介导肺 TRM 发育的新作用。
更新日期:2019-11-14
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