Dynamic landscapes and protective immunity coordinated by influenza-specific lung-resident memory CD8+ T cells revealed by intravital imaging
Lung tissue-resident memory CD8+ T-cells (Trm) are critical for heterosubtypic immunity against influenza virus-(IAV)-reinfection. How these cells surveil the lung, respond to infection and interact with other cells remains unresolved. Here, we used mouse models to identify and enrich lung Trm in combination with intravital and static imaging to assess spatiotemporal dynamics of IAV-induced lung TRM before and after recall-infection. CD69+CD103+ Trm localize to sites of prior influenza infection where they exhibit substantially slower movement properties than non-Trm that also surveil the lung. After rechallenge, lung Trm form tight clusters in an antigen-dependent manner. IAV-specific Trm express several factors that regulate myeloid cell biology and their protective immune responses are accompanied by activation and migration of dendritic cells to draining lymph nodes and recruitment of inflammatory monocytes. Overall, these data reveal the dynamic landscapes of lung Trm cells associated with early protective immunity against IAV infection. Overall design: The goal of this study is to assess the spatial, transcriptomic and functional properties of lung CD103+CD69+ tissue-resident CD8+ T cells. C57BL/6 mice were adoptively transferred with Thy1.1 P14 transgenic T cells (TCR-specific for LCMV GP33-41) and subsequently infected with influenza (PR8-GP33). Memory P14 cells were isolated from spleen (CD103-CD69- P14s) and lungs (CD103+CD69+ P14s) at day 26-30 post infection and sort purified directly in TRIzol. Comparative gene expression profiling analysis of RNA-seq data for lung CD103+CD69+ P14s and splenic CD103-CD69- cells