Fate mapped CD103+ resident memory T cells gradually seed the circulating memory T cell pool following acute infection 4550

Abstract

Abstract Description Memory T cells display heterogeneous migratory patterns. Some recirculate through the blood (TCIRC) while others reside within solid tissues (TRM). Classical models of memory T cell surveillance define TRM and TCIRC as distinct cellular lineages and presume that TRM are permanent residents of their host tissue, persisting there until death. However, recent evidence indicates that divisions between these subsets are not absolute, and some CD8+ TRM egress from their host tissues and join the TCIRC pool (termed ex-TRM). To precisely track the development and maintenance of ex-TRM, we are leveraging a mouse model in which tamoxifen administration permanently fluorescently labels cells expressing CD103, a marker of TRM in barrier tissues. When labeling is induced at a memory post-infection time point, labeled cells gradually accumulate in the blood, lymph nodes, spleen, and liver but decline or remain stable in barrier tissues. This suggests that as tissue-localized TRM naturally wane in the memory phase, they seed a portion of the TCIRC compartment with ex-TRM. These ex-TRM lose expression of some tissue residency markers, including CD103, but retain others, implying partial dedifferentiation from their residency programming. Measuring ex-TRM quality and quantity may provide a strategy to assess regional tissue immunity via blood samples. Ongoing studies are further characterizing ex-TRM ontogeny and differentiation and their functional relevance during recall responses. Funding Sources Supported by NIH 2R37AI084913 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)