Pulmonary antigen encounter regulates the establishment of tissue-resident CD8 memory T cells in the lung airways and parenchyma.
Pulmonary antigen encounter regulates the establishment of tissue-resident CD8 memory T cells in the lung airways and parenchyma.
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DOI：
10.1038/s41385-018-0003-x
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发表时间：
2018-07
影响因子：
8
通讯作者：
Kohlmeier JE
中科院分区：
文献类型：
--
作者：
McMaster SR;Wein AN;Dunbar PR;Hayward SL;Cartwright EK;Denning TL;Kohlmeier JE
肺实质（LP）和气道中的常驻记忆CD 8 T（TRM）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CD 8 TRM所需的因素，知识不足。在这里，我们证明，在其他组织中描述的机制，气道和LP CD 8 TRM的建立需要在肺同源抗原识别。系统性效应CD 8 T细胞可以响应局部炎症而被瞬时拉入肺中，然而这些效应细胞未能建立组织驻留，除非抗原存在于肺环境中。效应CD 8 T细胞与肺中同源抗原的相互作用导致组织滞留标志物CD 69和CD 103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TRM导致病毒清除率降低和异亚型流感攻击后死亡率增加，尽管循环记忆CD 8 T细胞数量相同。这些发现表明，肺抗原的遭遇是建立肺CD 8 TRM所必需的，并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。
Resident memory CD8 T (TRM) 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 TRM. Here we demonstrate that, in contrast to mechanisms described for other tissues, airway and LP CD8 TRM 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 TRM 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 TRM and may inform future vaccine strategies to generate robust cellular immunity against respiratory pathogens.