Influenza infection generates memory CD4 T cells that occupy a specific lung resident niche and mediate early in situ responses (49.21)

Abstract

Abstract Lung-resident T cells are uniquely poised to mediate early in situ responses to respiratory pathogens. We have previously identified a subset of lung-resident CD4 T cells that mediate optimal protective immunity to respiratory infection. Here, we have examined the mechanisms for the establishment of lung-resident memory CD4 T cells and their role in anti-viral responses. Using intravenous (iv) infusion of antibody to differentiate between cells in the lung interstitium and those accessible to the circulation, we discovered that a minor subset of lung αβ CD4 T and most γδ T cells are protected from iv antibody staining (protected subset) while the remaining αβ CD4 T cells are readily stained (accessible subset). The protected αβ CD4 T cell subset and γδ T cells similarly expressed increased levels of CD11a, CD69, CD103 and CCR6 as compared to the accessible subset. The protected population of αβ CD4 T cells is established through respiratory infection as it comprises less than 10% of αβ CD4 T cells in naïve animals but represents approximately 30% of lung cells in influenza immune mice during the memory stage. Once established, the protected memory αβ CD4 T cells along with γδ T cells produces IFN-γ and IL-17 in situ early after influenza rechallenge. Our results show that the lung CD4 T cell population is comprised of a circulating subset and a tissue-resident subset with the tissue resident αβ CD4 T and γδ T cells acting as early responders to respiratory infections.