Differentiation and dynamics of circulating and tissue-resident memory CD8 T cells in the lung

Abstract

Abstract Memory CD8 T cells are capable of providing robust heterosubtypic immunity to Influenza. In contrast to other tissues, relatively little is known about the differentiation and localization of the memory CD8 T cell subsets within the lung. We utilized intravital 2-photon microscopy of live mice to examine the real-time dynamics of circulating and/or resident memory (Trms) CD8 T cells in the lung. LCMV-induced transgenic P14 CD8 memory T cells, which are exclusively circulating, were highly motile, while Influenza-experienced P14s, which are comprised of both circulating and resident memory CD8 T cells, exhibited heterogenous motility patterns including both highly motile cells and those exhibiting a slow to moderate motility pattern. Selective depletion of circulating memory CD8 T cells resulted in the loss of highly motile cells, suggesting that lung CD8 Trms exhibit slow to moderate motility. Intranasal administration of cognate peptide or recombinant Influenza virus infection induced the arrest of a large number of LCMV-experienced circulating P14s in the lung shortly after administration in an antigen-specific manner. Interestingly, within 12–48 hours post stimulation, the majority of lung-residing LCMV-experienced circulating P14s became un-arrested and began a moderate scanning motility phenotype that persisted in a substantial fraction of P14s and correlated with the generation of secondary memory CD103+ Trms in the lung. Overall, these data shed light into the differentiation and dynamics of circulating and resident CD8 memory T cells in the lung.