The identity of human tissue-emigrant CD8+ T cells (scRNAseq, scTCRseq, bulk RNA-seq)

Lymphocyte migration is essential for adaptive immune surveillance. However, ourcurrent understanding of this process is rudimentary, because most human studieshave been restricted to immunological analyses of blood and various tissues. Toaddress this, we used an integrated approach to characterize tissue-emigrant immunecells in thoracic duct lymph (TDL). The most prevalent immune cells in human andnon-human primate efferent lymph were T cells. Cytolytic CD8+ T cell subsets witheffector-like epigenetic and transcriptional signatures were clonotypically skewed andselectively confined to the intravascular circulation, whereas non-cytolytic CD8+ T cellsubsets with stem-like epigenetic and transcriptional signatures predominated intissues and TDL. Moreover, these anatomically distinct gene expression profiles wererecapitulated within individual antigen-specific clonotypes, suggesting paralleldifferentiation programs independent of the expressed antigen receptor. Our collectivedataset provides a framework of the migratory immune system and defines the natureof tissue-emigrant CD8+ T cells that recirculate via TDL. scRNAseq and scTCRseq of 1) HIV-specific or CMV-specific CD8+ T-cells and 2) memory CD8+ T-cells between TDL and blood bulk RNA-seq of FACS sorted CD8+ Tcell memory subsets from human peripheral blood (samples re-used from GSE148234).