Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka, 589-8511, Japan.
Mucosal Immunol. 2020 Jan;13(1):161-171. doi: 10.1038/s41385-019-0224-7. Epub 2019 Nov 13.
Lung resident memory CD8 T cells (T) 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 T following influenza infection. We find that, during the initial appearance of lung T, 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 T development or maintenance. In contrast, a monocyte deficient pulmonary environment in CCR2 mice results in significantly less lung T 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 T development through direct interaction with T cells in the lung.
肺部驻留记忆 CD8 T 细胞（T 细胞）对于抵抗呼吸道病毒至关重要，但对于其发育所需的细胞相互作用知之甚少。本文中，我们描述了经典单核细胞对于流感感染后肺部 T 细胞建立的必要性。我们发现，在肺部 T 细胞最初出现时，单核细胞和树突状细胞是肺部携带流感抗原的 APC 中数量最多的。令人惊讶的是，在初始 T 细胞启动后耗尽树突状细胞不会影响肺部 T 细胞的发育或维持。相比之下，CCR2 小鼠中缺乏单核细胞的肺部环境会导致流感感染后肺部 T 细胞明显减少，尽管抗病毒效应反应或外周记忆池没有缺陷。成像显示，抗原特异性 T 细胞与肺部携带抗原的单核细胞直接相互作用，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。这些数据描述了肺部单核细胞通过与肺部 T 细胞的直接相互作用介导肺部 T 细胞发育的新作用。
