Age-Related Dynamics of Lung-Resident Memory CD8⁺ T Cells in the Age of COVID-19

Following respiratory viral infections or local immunizations, lung resident-memory T cells (T_RM) of the CD8 lineage provide protection against the same pathogen or related pathogens with cross-reactive T cell epitopes. Yet, it is now clear that, if homeostatic controls are lost following viral pneumonia, CD8 T_RM cells can mediate pulmonary pathology. We recently showed that the aging process can result in loss of homeostatic controls on CD8 T_RM cells in the respiratory tract. This may be germane to treatment modalities in both influenza and coronavirus disease 2019 (COVID-19) patients, particularly, the portion that present with symptoms linked to long-lasting lung dysfunction. Here, we review the developmental cues and functionalities of CD8 T_RM cells in viral pneumonia models with a particular focus on their capacity to mediate heterogeneous responses of immunity and pathology depending on immune status.