呼吸道病毒，特别是流感病毒严重威胁我国人民身体健康和公共卫生安全。病毒特异性CD4 T细胞在抗呼吸道病毒感染过程中发挥重要作用。由于肺脏具有独特的解剖学结构，病毒特异性CD4 T细胞可存在于肺泡、肺间质和肺血管中。本团队前期发现肺泡驻留病毒特异性CD4 T细胞为独特T细胞群体，其表型和功能不同于肺间质和肺血管中驻留的CD4 T细胞，并发挥重要免疫保护作用（Immunity 2016）。本原创性研究将在前期研究基础上，继续紧扣国际前沿，利用肺泡/血管内细胞同步标记技术、单细胞转录组学新方法、逆转录病毒TCR转基因小鼠等新技术和新模型，深入揭示肺泡驻留流感病毒特异性CD4 T细胞来源、稳态维持及肺脏不同CD4 T细胞群体的单细胞转录组学特征和异同，并阐明其保护作用机制。在填补肺脏区域感染免疫空白的同时，为疫苗设计提供新思路和新方法，满足我国新发突发呼吸道病毒感染防控的需求。

Respiratory viruses, especially influenza virus represent major threats to public health. Viral-specific CD4 T cells play critical roles against respiratory viral infections. Lung has a unique anatomic structure, virus-specific CD4 T cells can reside in alveolar/airway, parenchyma and pulmonary vasculature. Our previous study showed that viral-specific CD4 T cells in the alveolar were a distinct CD4 T cell population. They were phenotypically and functionally different from CD4 T cells in parenchyma and pulmonary vasculature and were required for protection. In the current study, state of the art technologies will be utilized, such as Simultaneous Intranasal/Intravascular Antibody Labeling, Single cell RNA-seq and TCR Retrogenic mice, to uncover the origin and homeostasis of alveolar viral-specific T cells, to compare the differences of transcriptomic signature at single cell level and to decipher the mechanisms for protection. This study will provide new insight into vaccine development against respiratory viruses and help to prevent and control potential emerging respiratory virus epidemics in China.