The human lung harbors a large population of resident memory T cells (Trm cells). These cells are perfectly positioned to mediate rapid protection against respiratory pathogens such as influenza virus, a highly contagious respiratory pathogen that continues to be a major public health burden. Animal models show that influenza-specific lung CD8⁺ Trm cells are indispensable for crossprotection against pulmonary infection with different influenza virus strains. However, it is not known whether influenza-specific CD8⁺ Trm cells present within the human lung have the same critical role in modulating the course of the disease. Here, we showed that human lung contains a population of CD8⁺ Trm cells that are highly proliferative and have polyfunctional progeny. We observed that different influenza virus–specific CD8⁺ T cell specificities differentiated into Trm cells with varying efficiencies and that the size of the influenza-specific CD8⁺ T cell population persisting in the lung directly correlated with the efficiency of differentiation into Trm cells. To our knowledge, we provide the first ex vivo dissection of paired T cell receptor (TCR) repertoires of human influenza–specific CD8⁺ Trm cells. Our data reveal diverse TCR profiles within the human lung Trm cells and a high degree of clonal sharing with other CD8⁺ T cell populations, a feature important for effective T cell function and protection against the generation of viral-escape mutants.

中文翻译：

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流感特异性肺驻留记忆T细胞具有增殖性和多功能性，并维持多种TCR谱

人肺具有大量的常驻记忆T细胞（Trm细胞）。这些细胞处于良好的位置，可以介导对呼吸道病原体（如流感病毒）的快速保护，流感病毒是一种高度传染性的呼吸道病原体，仍然是主要的公共卫生负担。动物模型显示，流感特异性肺CD8 ⁺ Trm细胞对于交叉保护不同流感病毒株的肺部感染是必不可少的。但是，尚不知道人肺中存在的流感特异性CD8 ⁺ Trm细胞在调节疾病过程中是否具有相同的关键作用。在这里，我们表明人肺中含有CD8 ⁺Trm细胞高度增殖并具有多功能子代。我们观察到，不同的流感病毒特异性CD8 ⁺ T细胞特异性分化为具有不同效率的Trm细胞，并且流感特异性CD8 ⁺ T细胞群体在肺中持续存在的大小与分化为Trm细胞的效率直接相关。据我们所知，我们提供了人类流感特异性CD8 ⁺ Trm细胞的配对T细胞受体（TCR）组成部分的首次离体解剖。我们的数据揭示了人肺Trm细胞内各种TCR谱以及与其他CD8 ^+的高度克隆共享 T细胞群体，对于有效的T细胞功能和防止病毒逃逸突变体的产生很重要的功能。