Abstract
Lung-tissue-resident memory (TRM) CD8+ T cells are critical for heterosubtypic immunity against influenza virus (IAV) reinfection. How TRM 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 TRM cells before and after recall infection. CD69+CD103+ TRM cells preferentially localized to lung sites of prior IAV infection, where they exhibited patrolling behavior. After rechallenge, lung TRM cells formed tight clusters in an antigen-dependent manner. Transcriptomic analysis of IAV-specific TRM cells revealed the expression of several factors that regulate myeloid cell biology. In vivo rechallenge experiments demonstrated that protection elicited by TRM 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 TRM cells that mediate early protective immunity against IAV infection.