Human lungs maintain tissue-resident memory T cells against a broad spectrum of pathogens
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Nature Immunology
Authors: 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, Judith Cave, Aiman Alzetani, Edwin Woo, Elizabeth Phillips, Simon Mallal, Alba Grifoni, Benjamin J. Schmiedel, Alessandro Sette, Bjoern Peters, Christian H. Ottensmeier, Pandurangan Vijayanand
Institutions: La Jolla Institute for Immunology, University of California San Diego, University of Liverpool, Liverpool Heart and Chest Hospital NHS Trust, Liverpool Heart and Chest Hospital, University Hospital Southampton NHS Foundation Trust, Vanderbilt University Medical Center, Clatterbridge Cancer Centre NHS Foundation Trust
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7171501458