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<p>Lung tissue-resident memory T (T<sub>RM</sub>) 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 T<sub>RM</sub> 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 T<sub>RM</sub> cells specific to multiple pathogens. We confirmed that a large fraction of lung T<sub>RM</sub> 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 T<sub>RM</sub> cells, suggesting that strategies to bolster these responses could provide durable protection against severe lung infections.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月28日

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  • 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

摘要

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.