Expression of CD45RA on tissue resident memory T cells in the lung identifies a transcriptionally distinct population 2334756

Introduction Expression of CD45RA has been used to identify naïve T cells and a subpopulation of memory T cells which re-express CD45RA (TEMRAs). TEMRA cells have previously been characterized in the peripheral blood, however the expression of CD45RA has not been evaluated on resident memory T cells in the lung, nor has a CD45RA-positive gene expression profile been previously described in the lung environment. Methods Matched PBMC and BAL samples from lung transplant recipients were stained with CITE-seq antibodies to identify the single-cell transcriptional profile of CD45RA-positive T cells in each compartment Results CD45RA-positive resident memory T cells in the lung were transcriptionally distinct from circulating TEMRAs, producing spatially distinct clusters. CD45RA+ T cells in the lung expressed canonical markers of residence, including constitutive CD69 expression and ITGA1 positivity. Furthermore, lung-resident CD45RA+ CD8+ T cells expressed high levels of cytotoxic cytokines including granzyme A and granzyme K. Conclusion These data provide new evidence of a distinct resident memory T cell population in the lung. These cells represent a potential pathogenic contributor to lung transplant rejection, offering a potential therapeutic target for intervention.