Tissue-resident memory T cells (T_RM) in the lungs are pivotal for protection against repeated infection with respiratory viruses. However, the gradual loss of these cells over time and the associated decline in clinical protection represent a serious limit in the development of efficient T cell based vaccines against respiratory pathogens. Here, using an adenovirus expressing influenza nucleoprotein (AdNP), we show that CD8 T_RM in the lungs can be maintained for at least 1 year post vaccination. Our results reveal that lung T_RM continued to proliferate in situ 8 months after AdNP vaccination. Importantly, this required airway vaccination and antigen persistence in the lung, as non-respiratory routes of vaccination failed to support long-term lung T_RM maintenance. In addition, parabiosis experiments show that in AdNP vaccinated mice, the lung T_RM pool is also sustained by continual replenishment from circulating memory CD8 T cells that differentiate into lung T_RM, a phenomenon not observed in influenza-infected parabiont partners. Concluding, these results demonstrate key requirements for long-lived cellular immunity to influenza virus, knowledge that could be utilized in future vaccine design.

肺部的组织驻留记忆 T 细胞 ( _TRM ) 是防止呼吸道病毒反复感染的关键。然而，随着时间的推移，这些细胞逐渐丢失以及相关的临床保护作用下降严重限制了开发针对呼吸道病原体的有效 T 细胞疫苗。在这里，使用表达流感核蛋白 (AdNP) 的腺病毒，我们表明肺部的 CD8 T _RM可以在疫苗接种后维持至少 1 年。我们的结果表明肺TRM 在_AdNP疫苗接种后 8 个月继续原位增殖。重要的是，这需要气道疫苗接种和肺部抗原持久性，因为非呼吸道疫苗接种途径无法支持长期肺 T_RM维护。此外，异种共生实验表明，在 AdNP 疫苗接种的小鼠中，肺 T _RM池也通过循环记忆 CD8 T 细胞的持续补充来维持，这些细胞分化为肺 T _RM，这种现象在感染流感的副生物伙伴中没有观察到。总之，这些结果证明了对流感病毒的长期细胞免疫的关键要求，这些知识可用于未来的疫苗设计。