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

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

Stephanie van de Wall, Scott M. Anthony, Lisa S. Hancox, Lecia L. Pewe, Ryan A. Langlois, Dietmar Zehn, Vladimir P. Badovinac and John T. Harty
Immunity (Cambridge, Mass.), Vol.57(8), pp.1878-1892.e5
07/13/2024
DOI: 10.1016/j.immuni.2024.06.016
PMCID: PMC12001675
PMID: 39043185
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC12001675/pdf/nihms-2048276.pdfView
Open Access

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. [Display omitted] •Intravital microscopy reveals patrolling behavior and movements of CD103+ TRM cells•CD103+ TRM cells persist in the lung near sites of prior influenza infection•At rechallenge, CD103+ TRM cells cluster near IAV-infected cells in an Ag-specific manner•Lung CD103+ TRM cells control myeloid cell influx, in part through IFN-γ production Due to technical constraints, how memory T cells surveil the lung is not understood. Using intravital microscopy, van de Wall et al. demonstrate the unique surveillance properties of CD103+ TRM cells in the lungs of influenza-experienced mice. Upon antigen re-encounter, lung TRM cells cluster at infection sites and promote myeloid cell influx.
influenza virus intravital imaging lung T resident memory

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