Enhanced survival of lung tissue-resident memory CD8+ T cells during infection with influenza virus due to selective expression of IFITM3

Infection with influenza virus results in the deposition of anti-influenza CD8(+) resident memory T cells (T-RM cells) in the lung. As a consequence of their location in the lung mucosal tissue, these cells are exposed to cytopathic pathogens over the life of the organism and may themselves be susceptible to infection. Here we found that lung T-RM cells selectively maintained expression of the interferon-induced transmembrane protein IFITM3, a protein that confers broad resistance to viral infection. Lung T-RM cells that lacked IFITM3 expression were more susceptible to infection than were their normal counterparts and were selectively lost during a secondary bout of infection. Thus, lung T-RM cells were programmed to retain IFITM3 expression, which facilitated their survival and protection from viral infection during subsequent exposures.