Resident memory CD8 T (T_RM) cells in the lung parenchyma (LP) and airways provide heterologous protection against influenza virus challenge. However, scant knowledge exists regarding factors necessary to establish and maintain lung CD8 T_RM. Here we demonstrate that, in contrast to mechanisms described for other tissues, airway, and LP CD8 T_RM establishment requires cognate antigen recognition in the lung. Systemic effector CD8 T cells could be transiently pulled into the lung in response to localized inflammation, however these effector cells failed to establish tissue residency unless antigen was present in the pulmonary environment. The interaction of effector CD8 T cells with cognate antigen in the lung resulted in increased and prolonged expression of the tissue-retention markers CD69 and CD103, and increased expression of the adhesion molecule VLA-1. The inability of localized inflammation alone to establish lung T_RM resulted in decreased viral clearance and increased mortality following heterosubtypic influenza challenge, despite equal numbers of circulating memory CD8 T cells. These findings demonstrate that pulmonary antigen encounter is required for the establishment of lung CD8 T_RM and may inform future vaccine strategies to generate robust cellular immunity against respiratory pathogens.

中文翻译：

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肺抗原遭遇调节组织驻留 CD8 记忆 T 细胞在肺气道和实质中的建立。

肺实质 (LP) 和气道中的常驻记忆 CD8 T (T _RM ) 细胞提供针对流感病毒攻击的异源保护。_{然而，关于建立和维持肺 CD8 T RM}的必要因素知之甚少。在这里，我们证明，与针对其他组织、气道和 LP CD8 T _{RM描述的机制相比}建立需要肺中的同源抗原识别。全身效应 CD8 T 细胞可以响应局部炎症而被瞬时拉入肺部，但是这些效应细胞无法建立组织驻留，除非肺部环境中存在抗原。效应 CD8 T 细胞与肺中同源抗原的相互作用导致组织保留标记 CD69 和 CD103 的表达增加和延长，以及粘附分子 VLA-1 的表达增加。局部炎症无法单独建立肺 T _RM尽管循环记忆 CD8 T 细胞数量相等，但在异型流感攻击后导致病毒清除率降低和死亡率增加。这些发现表明，肺部抗原接触是建立肺部 CD8 T _RM所必需的，并且可能为未来的疫苗策略提供信息，以产生针对呼吸道病原体的强大细胞免疫力。