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

By P. Szabo, H. M. Levitin, Michelle Miron, M. Snyder, T. Senda, Jinzhou Yuan, Y. Cheng, Erin Bush, P. Dogra, Puspa Thapa and 2 more. Nature Communications, 2019

627 citations recorded by the source corpus.

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. Immune cells are shaped by the tissue environment, yet the states of healthy human T cells are mainly studied in the blood. Here, the authors perform single cell RNA-seq of T cells from tissues and blood of healthy donors and show its utility as a reference map for comparison of human T cell states in disease.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7afac667b4c9d18d0cba59224bdc0993c4b3ef53

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In Immunology

1. Zemin Zhang
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1. Krzysztof Polanski
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Citations in the corpus

• Cross-tissue immune cell analysis reveals tissue-specific features in humans (2022, background): “We previously reported single-cell RNA sequencing (scRNA-seq) analysis of T cells in three tissues from two donors (20), identifying tissue-specific signatures.”
• Pan-cancer single-cell landscape of tumor-infiltrating T cells (2021, background): “The ISG Treg cells were located at the center of the trajectory, suggesting that a fraction of Treg cells responded to type I interferons in TME during activation, which is consistent with a recent report suggesting high ISG as a feature of intermediate state during CD4 T cell activation (29).”