Circulating KLRG1+ memory T cells retain the flexibility to become tissue-resident

KLRG1+ CD8 T cells persist for months after clearance of acute infections and maintain high levels of effector molecules, contributing protective immunity against systemic pathogens. Upon secondary infection, these long-lived effector cells (LLECs) are incapable of forming other circulating KLRG1− memory subsets such as central and effector memory T cells. Thus, KLRG1+ memory T cells are frequently referred to as a terminally differentiated population that is relatively short lived. Here, we show that following viral infection of mice, effector cells derived from LLEC rapidly enter nonlymphoid tissues and reduce pathogen burden, but are largely dependent on receiving antigen cues from vascular endothelial cells. Single-cell RNA sequencing revealed that secondary memory cells in nonlymphoid tissues arising from either KLRG1+ or KLRG1− memory precursors developed a similar transcriptional signature. Thus, although LLEC cannot differentiate into other circulating memory populations, they still retain the flexibility to enter tissues and establish residency. Secondary P14 memory cells from C57Bl/6 mice infected with LCMV-Armstrong were isolated by Fluorescence activated cell sorting (FACS) from different tissue sites (spleen, lymph nodes, small intestine and kidney. Cells were stained with TotalSeq-A antibodies and hashtagged before pooling for library construction and sequencing. Please note that as de-multiplexed files are unavailable for each sample, each sample record represents mixed-sample (of LLEC, TCM, TEM from spleen, lymph nodes, small intestine and kidney; 12 samples). Each of processed data file (the GEX text file, HTO text file, ADT text file and the SeuratObject_metadata text file) have information on all 12 samples, as detailed in the readme.txt.