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.