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

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.

SUBMITTER: Szabo PA

PROVIDER: S-EPMC6797728 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Szabo Peter A PA Levitin Hanna Mendes HM Miron Michelle M Snyder Mark E ME Senda Takashi T Yuan Jinzhou J Cheng Yim Ling YL Bush Erin C EC Dogra Pranay P Thapa Puspa P Farber Donna L DL Sims Peter A PA

Nature communications 20191017 1

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 ...[more]

PMID: 31624246

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

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

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