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A single cell reference map for human blood and tissue T cell activation

ABSTRACT: Human T cells coordinate adaptive immunity by localization in diverse tissue sites, though blood T cells are the most readily studied. We investigated the functional responses of T cells isolated from human lungs (LG), lymph nodes (LN), bone marrow (BM), and blood to TCR-stimulation using single-cell RNA-seq. We defined cellular states for resting T cells including signatures that differentiate tissue and blood T cells and employed new factorization methods to identify activation states conserved across tissues, including an IFN-response activation state in CD4+T cells and distinct effector states specific to CD8+T cells. We demonstrate how this high-resolution map can be used to assess the origin and functional state of T cells in disease by projecting scRNAseq profiles of tumor-associated T cells from multiple cancers, revealing CD8 T cells that co-express markers of exhaustion, activation, and proliferation, and a lack of activated CD4 T cells. Our results establish a high-dimensional reference for human T cell homeostasis and function in multiple sites, from which to probe T cell dysfunction in disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE126030 | GEO | 2019/09/09

REPOSITORIES: GEO

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