Defining the abundance, fate, and function of secondary lymphoid organ resident memory T cells

Abstract For sixty years we have understood that lymphocytes recirculate through blood and secondary lymphoid organs (SLO). Recently, it has been observed that SLOs contain resident populations of memory T cells. Here, we show that conventional isolation techniques grossly underestimate the proportion of SLO CD8+ T RM,and resident cells constitute a substantial fraction of regionalized immunity within LNs. We found that SLO T RMare very long-lived in mice and persist for >500 days after a single infection with LCMV Armstrong. Using a variety of infection models, we observed that the location of primary infection biased the density of SLO T RMto specific draining LNs. Moreover, SLO T RMexpressed a phenotypic relationship with T RMin specific upstream nonlymphoid tissues, and remarkably, retained durable expression of regional homing markers. Upon reactivation, mesenteric LN derived SLO T RMpreferentially homed to the small intestine compared to T CM. Thus, T RMcomprise a substantial fraction of LN memory CD8+ T cells, are refractory to isolation, can be remarkably durable, retain tissue-specific homing potential in the event of reactivation, and likely comprise an underappreciated and underestimated contributor to LN immune surveillance and regional anamnestic immune responses. Supported by fellowship from the University of Minnesota - Department of Microbiology and Immunology Dennis W. Watson Fellowship