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

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. Unlike in other tissues, lung-resident memory T cell populations are not well maintained in mice. Here the authors show that this is not the case in human lungs, where tissue-resident memory T cells specific to a variety of pathogens can persist for many years.

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Publication Details

Journal
Nature Immunology
Published
2026-07-28
DOI
https://doi.org/10.1038/s41590-026-02592-6
Primary Topic
T-cell and B-cell Immunology
Type
article
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article

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

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Nature Immunology
T-cell and B-cell Immunology
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Human lungs maintain tissue-resident memory T cells against a broad spectrum of pathogens

Vicente Fajardo, Alessandro Sette, Pandurangan Vijayanand, Aiman Alzetani, Monalisa Mondal, Bjoern Peters, Isabel Marchand-Casas, Lindsey Chudley, Michael Shackcloth, Aquib Ehtram, Simon Alexander Mallal, Benjamin Joachim Schmiedel, Christian H. Ottensmeier, Alba Grifoni, Francisco Emmanuel Castañeda-Castro, Zubin Roy, Edwin Woo, Elizabeth Phillips, Celia Ferrández Alaminos, Judith Cave, Serena J. Chee
article en

Abstract

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. Unlike in other tissues, lung-resident memory T cell populations are not well maintained in mice. Here the authors show that this is not the case in human lungs, where tissue-resident memory T cells specific to a variety of pathogens can persist for many years.

Nature ImmunologyVol. 27(8)
La Jolla Institute for Immunology (US), University of Liverpool (GB), Liverpool Heart and Chest Hospital NHS Trust (GB), University Hospital Southampton NHS Foundation Trust (GB), Clatterbridge Cancer Centre NHS Foundation Trust (GB), University of California San Diego (US), Liverpool Heart and Chest Hospital (GB), Vanderbilt University Medical Center (US)
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