New research led by scientists at La Jolla Institute for Immunology and the University of Liverpool provides the first comprehensive look at how a hidden immune cell army defends human lungs, according to a Jul. 28 report. The study, published in Nature Immunology, shows that human lung tissue serves as a reservoir for large numbers of tissue-resident memory T cells (TRM cells), which are prepared to combat various viruses, bacteria, and fungal pathogens.
The researchers found that these TRM cells reside only in the lungs and do not appear in blood samples. While these cells can persist for years in human lung tissue, they do not last as long in mice—a common model used in preclinical research. This difference highlights the importance of studying human samples directly when developing vaccines targeting respiratory infections.
For their study, the team examined more than 87,000 lung TRM cells from 40 participants aged 61 to 83. This allowed them to analyze how past vaccinations and lifelong exposure to pathogens shape TRM populations within the lungs. Many participants had TRM cells ready to respond to common respiratory viruses such as influenza type A, SARS-CoV-2, parainfluenza virus, respiratory syncytial virus (RSV), and metapneumovirus (MPV). Additionally, some had T cells targeting herpesviruses like cytomegalovirus (CMV) and Epstein Barr virus (EBV), as well as Bordetella pertussis—the bacterium responsible for whooping cough—and even Aspergillus fumigatus fungus.
Lead researcher Vijayanand said that responses observed in lung tissue are not seen in circulating blood T cells: "An important next step is to study how vaccination impacts TRM cells in the lungs," said Vijayanand. "We need to assess more samples, including samples from donors who recently received vaccines."
The findings suggest that vaccine researchers may need to examine lung T cell responses directly rather than relying solely on blood tests when designing strategies against severe respiratory infections.
