Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory CD8⁺ T Cells

Respiratory virus infections, such as those mediated by influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for substantial morbidity and mortality, especially in children and older adults. Furthermore, the potential emergence of highly pathogenic strains of influenza virus poses a significant public health threat. Thus, the development of vaccines capable of eliciting long-lasting protective immunity to those pathogens is a major public health priority. CD8⁺ Tissue-resident memory T (T_RM) cells are a newly defined population that resides permanently in the nonlymphoid tissues including the lung. These cells are capable of providing local protection immediately after infection, thereby promoting rapid host recovery. Recent studies have offered new insights into the anatomical niches that harbor lung CD8⁺ T_RM cells, and also identified the requirement and limitations of T_RM maintenance. However, it remains controversial whether lung CD8⁺ T_RM cells are continuously replenished by new cells from the circulation or permanently lodged in this site. A better understanding of how lung CD8⁺ T_RM cells are generated and maintained and the tissue-specific factors that drive local T_RM formation is required for optimal vaccine development. This review focuses on recent advance in our understanding of CD8⁺ T_RM cell establishment and maintenance in the lung, and describes how those processes are uniquely regulated in this tissue.