Formation, flexibility, and function of long-lived effector cells 3815

Abstract Description KLRG1+ long-lived effector cells (LLECs), are CD8 T cells that persist in the blood and spleen for months and contribute robust protective immunity against systemic infection. We asked whether LLEC (or their progeny) ever leave the blood stream to combat tissue-restricted infections like influenza, and whether they could generate resident memory T cells (TRM). We found that effector cells derived from LLECs rapidly enter nonlymphoid tissues and reduce pathogen burden but show dependence on antigen presentation by vascular endothelial cells. Flow cytometry and single-cell RNA sequencing revealed that secondary memory cells arising from any memory precursor develop a similar resident memory phenotype and transcriptional signature. These data lead us to conclude that despite other limits on their differentiation, LLECs retain the ability to enter non-lymphoid tissues and establish residency. In specific pathogen free mice exposed to a single acute infection, LLECs tend to fade over time. However, in mice which are first exposed to natural commensals and pathogens through cohousing with pet store mice, LLECs dominate the memory CD8 T cell pool. We find that increased production of short-lived effector cells followed by a diminished contraction phase improves formation of LLEC. Current work tests whether noncanonical cytokines or conversion from other memory subsets supports LLEC in cohoused mice, potentially revealing new strategies for memory T cell persistence. Funding Sources This work was supported by NIH/NIAID: R01AI155468 and F32AI178962 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)