Dynamic landscapes and protective immunity coordinated by influenza-specific lung-resident memory CD8⁺ T cells revealed by intravital imaging

Lung-tissue-resident memory (T_RM) CD8⁺ T cells are critical for heterosubtypic immunity against influenza virus (IAV) reinfection. How T_RM cells surveil the lung, respond to infection, and interact with other cells remains unresolved. Here, we used IAV infection of mice in combination with intravital and static imaging to define the spatiotemporal dynamics of lung T_RM cells before and after recall infection. CD69⁺CD103⁺ T_RM cells preferentially localized to lung sites of prior IAV infection, where they exhibited patrolling behavior. After rechallenge, lung T_RM cells formed tight clusters in an antigen-dependent manner. Transcriptomic analysis of IAV-specific T_RM cells revealed the expression of several factors that regulate myeloid cell biology. In vivo rechallenge experiments demonstrated that protection elicited by T_RM cells is orchestrated in part by interferon (IFN)-γ-mediated recruitment of inflammatory monocytes into the lungs. Overall, these data illustrate the dynamic landscapes of CD103⁺ lung T_RM cells that mediate early protective immunity against IAV infection.