Continuous, antigen independent re-seeding of lung resident memory CD8+ T-cells after Influenza A virus infection.

Abstract

Abstract Resident memory CD8+ T-cells (Trm) are a subset of memory T-cells, defined by their permanent localization in non-lymphoid tissues and are associated with potent protection against local infections. Lung Trm can mediate rapid control of respiratory pathogens like influenza A Virus (IAV), but in contrast to other non-lymphoid tissues like the skin, the number of lung Trm is not maintained long term. Here we observed through intranasal CFSE labeling that CD69+/CD103+ memory CD8 T-cell reside in the lung parenchyma longer then their CD69−/CD103− counterparts, but the average residence time of a Trm cell in the lung parenchyma is less than a week. We show that, in contrast to skin, Trm in the lung are prone to apoptosis and require continuous recruitment of memory CD8 T-cells from the circulation to maintain their numbers. Of note, the lung microenvironment drives the continuous conversion of circulating memory CD8+ T-cells into Trm, but does not require the presence of antigen in the lung. Moreover, intrinsic changes to the circulating memory CD8 T-cell population over time decrease their capacity to adopt a Trm phenotype. Thus our data could provide an explanation as to why lung Trm are not maintained long term.