Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice

Lung tissue-resident memory T cells (T_RM) are critical for the local control of respiratory tract infections caused by influenza A viruses (IAV). Here we compare T_RM populations induced by intranasal adenoviral vector vaccines encoding hemagglutinin and nucleoprotein (NP) with those induced by an H1N1 infection in BALB/c mice. While vaccine-induced T_RM express high levels of CD103 and persist longer in the lung parenchyma, short-lived, H1N1-induced T_RM have a transcriptome associated with higher cytotoxic potential and distinct transcriptional profile as shown by single-cell RNA sequencing. In both the vaccine and H1N1 groups, NP-specific CD8⁺ T cells expand during heterologous influenza virus infection and protect the mice from disease. Meanwhile, lung inflammation in response to an infection with unrelated respiratory syncytial virus do not influence the fate of pre-existing T_RM. Our preclinical work thus confirms that inflammatory conditions in the tissue shape the phenotypic and functional characteristics of T_RM to serve relevant informations for optimizing mucosal vaccines.