Researchers have identified a specific population of immune cells residing within human lung tissue that provides durable, long-term defense against a wide range of respiratory viruses, bacteria, and fungi. According to a Nature Immunology study led by scientists at the La Jolla Institute for Immunology (LJI) and the University of Liverpool, human lung tissue serves as a biological reservoir for a large number of tissue-resident memory T cells, known as TRM cells.
Lung Immune Cells Provide Long-Lasting Defense Against Pathogens
These specialized cells are prepared to combat various pathogens directly in the respiratory tract. This study highlights the power of investigating immune cells from humans,
said Pandurangan Vijayanand, LJI William K Bowes distinguished professor, in a news release. Unlike circulating immune cells, lung TRM cells reside exclusively in the lungs and do not appear in standard peripheral blood samples, which explains why their protective potential remained largely hidden during decades of conventional immunology research.
Pathogen Specificities and Human Tissue Mapping
The study analyzed more than 87,000 lung TRM cells obtained from 40 human participants ranging in age from 61 to 83. This age span allowed researchers to observe how lifelong exposure to pathogens and past immunizations shaped the immune cells within the respiratory system.
The cross-sectional lung cohort comprised individuals undergoing standard-of-care surgical resection for primary lung non-small-cell lung cancer at Liverpool Heart and Chest NHS Foundation Trust Hospital and University Hospital Southampton NHS Foundation Trust. Ethical approval for the research was obtained from the South Central – Hampshire A Research Ethics Committee and the LJI Ethics Committee, with written informed consent collected from all participants prior to intraoperative sample collection.
The analysis revealed that many participants harbored TRM cells ready to respond to five common respiratory viruses: * Influenza type A * SARS-CoV-2 * Parainfluenza virus * Respiratory syncytial virus (RSV) * Metapneumovirus
In addition to respiratory viruses, the researchers identified T cells targeting two herpesviruses—cytomegalovirus and Epstein-Barr virus—as well as Bordetella pertussis, the bacterium responsible for whooping cough. Some participants also possessed TRM cells capable of responding to Aspergillus fumigatus, a common fungus that can cause life-threatening infections in immunocompromised patients.
Implications for Animal Models and Vaccine Design
The findings highlight significant limitations in preclinical research models. While these specialized immune cells can persist in human lung tissue for years, they undergo rapid attrition in mice, which are frequently utilized as a standard model in preclinical testing. Because of these distinct biological differences between species, the study authors emphasize that future translational studies and preclinical vaccine evaluations should prioritize direct human lung tissue samples.
The research suggests that future vaccine development may need to focus specifically on boosting lung-resident T cells rather than relying solely on blood sample analyses to measure immune protection. An important next step is to study how vaccination impacts TRM cells in the lungs,
Vijayanand stated, noting the necessity of assessing samples from donors who have recently received immunizations to better understand and achieve more effective, long-lasting defense against severe respiratory infections.
