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Human lungs maintain tissue-resident memory T cells against a broad spectrum of pathogens
Journal article   Open access   Peer reviewed

Human lungs maintain tissue-resident memory T cells against a broad spectrum of pathogens

Vicente Fajardo-Rosas, Aquib Ehtram, Isabel Marchand-Casas, Serena J. Chee, Monalisa Mondal, Celia Ferrández Alaminos, Francisco Emmanuel Castañeda-Castro, Zubin Roy, Lindsey Chudley, Michael Shackcloth, …
Nature immunology, Vol.27(8), pp.1749-1761
2026
DOI: https://doi.org/10.1038/s41590-026-02592-6
PMID: 42521848
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Published57.68 MBDownloadView
Open Access CC BY-NC-ND V4.0

Abstract

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Lung tissue-resident memory T (TRM) cells are critical for frontline immunity, yet they undergo rapid attrition in the mouse lung. Whether this paradigm applies to humans has remained unknown. Here we present a comprehensive analysis of T cells from human lungs, characterizing the prevalence and properties of lung TRM cells specific to a broad spectrum of pathogens. Using a T cell receptor-guided approach that integrates single-cell transcriptomics with paired T cell receptor repertoire profiling, we mapped the pathogen specificity of more than 87,000 lung T cells across 40 individuals, the majority of whom harbored TRM cells specific to multiple pathogens. We confirmed that a large fraction of lung TRM clones persist in the lung for many months to years. Thus, in contrast to those of mice, human lungs retain a stable and varied pool of pathogen-specific TRM cells, suggesting that strategies to bolster these responses could provide durable protection against severe lung infections.

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