Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease

Peter A. Szabo, Hanna Mendes Levitin, Michelle Miron, Mark E. Snyder, Takashi Senda, Jinzhou Yuan, Yim Ling Cheng, Erin C. Bush, Pranay Dogra, Puspa Thapa, Donna L. Farber () and Peter A. Sims ()
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Peter A. Szabo: Columbia Center for Translational Immunology, Columbia University Irving Medical Center
Hanna Mendes Levitin: Columbia University Irving Medical Center
Michelle Miron: Columbia Center for Translational Immunology, Columbia University Irving Medical Center
Mark E. Snyder: Columbia Center for Translational Immunology, Columbia University Irving Medical Center
Takashi Senda: Columbia Center for Translational Immunology, Columbia University Irving Medical Center
Jinzhou Yuan: Columbia University Irving Medical Center
Yim Ling Cheng: Columbia University Irving Medical Center
Erin C. Bush: Columbia University Irving Medical Center
Pranay Dogra: Columbia Center for Translational Immunology, Columbia University Irving Medical Center
Puspa Thapa: Columbia Center for Translational Immunology, Columbia University Irving Medical Center
Donna L. Farber: Columbia Center for Translational Immunology, Columbia University Irving Medical Center
Peter A. Sims: Columbia University Irving Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-12464-3

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