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

Nat Commun. 2019 Oct 17;10(1):4706. doi: 10.1038/s41467-019-12464-3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Humans
  • Lung / metabolism*
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mucous Membrane / immunology
  • Mucous Membrane / metabolism
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Single-Cell Analysis / methods*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transcriptome / genetics*