Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-019-12464-3
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Funding
- US National Institutes of Health (NIH) [AI128949, AI106697]
- American Association of Immunologists (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists
- NIH [S10RR027050]
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Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8(+) T cells and an interferon-response state for CD4(+) T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8(+) compared to CD4(+) T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease.
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