Abstract
Following respiratory viral infections or local immunizations, lung resident-memory T cells (TRM) 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 TRM cells can mediate pulmonary pathology. We recently showed that the aging process can result in loss of homeostatic controls on CD8 TRM 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 TRM cells in viral pneumonia models with a particular focus on their capacity to mediate heterogeneous responses of immunity and pathology depending on immune status.
Highlights
“Infectious diseases are no respecters of wealth, power, or personal merit
While the resident CD4:CD8 memory T cell ratios vary by compartment, 20–50% of pulmonary CD8 T cells expected to be critical for anti-viral memory responses, display a recently activated phenotype indicated by HLA-DR antigen on their surface [22, 25, 26], suggesting active vigilance
Our results found that TRM cells isolated from aged lungs lack a subpopulation characterized by high expression of molecules involved in T Cell Receptor (TCR) signaling and effector function [6]
Summary
Following respiratory viral infections or local immunizations, lung resident-memory T cells (TRM) of the CD8 lineage provide protection against the same pathogen or related pathogens with cross-reactive T cell epitopes. It is clear that, if homeostatic controls are lost following viral pneumonia, CD8 TRM cells can mediate pulmonary pathology. We recently showed that the aging process can result in loss of homeostatic controls on CD8 TRM cells in the respiratory tract. This may be germane to treatment modalities in both influenza and coronavirus disease 2019 (COVID-19) patients, the portion that present with symptoms linked to long-lasting lung dysfunction.
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