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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 | Peter A Sims
Nature communications | 2019

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.

Pubmed ID: 31624246

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: P01 AI106697
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI106711
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008224
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI128949

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