Journal Article

Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes

Labourdette, Delphine, Pont, Fréderic, Pizzolato, Gabriele, Merville, Pierre, Déchanet-Merville, Julie, Kaminski, Hannah, Martins, Fréderic, Ysebaert, Loic, Fournié, Jean-Jacques, Poupot, Mary, Quillet-Mary, Anne, Laurent, Camille, Tosolini, Marie, Franchini, Don-Marc, Meraviglia, Serena, Cadot, Sarah, Milpied, Pierre, Valle, Carine, Dieli, Francesco

2019

Overview

gamma delta T lymphocytes represent similar to 1% of human peripheral blood mononuclear cells and even more cells in most tissues of vertebrates. Although they have important anticancer functions, most current single-cell RNA sequencing (scRNA-seq) studies do not identify gamma delta T lymphocytes because their transcriptomes at the single-cell level are unknown. Here we show that high-resolution clustering of large scRNA-seq datasets and a combination of gene signatures allow the specific detection of human gamma delta T lymphocytes and identification of their T cell receptor (TCR)V delta 1 and TCRV delta 2 subsets in large datasets from complex cell mixtures. In t-distributed stochastic neighbor embedding plots from blood and tumor samples, the few gamma delta T lymphocytes appear collectively embedded between cytotoxic CD8 T and NK cells. Their TCRV delta 1 and TCRV delta 2 subsets form close yet distinct subclusters, respectively neighboring NK and CD8 T cells because of expression of shared and distinct cytotoxic maturation genes. Similar pseudotime maturation trajectories of TCRV delta 1 and TCRV delta 2 gamma delta T lymphocytes were discovered, unveiling in both subsets an unattended pool of terminally differentiated effector memory cells with preserved proliferative capacity, a finding confirmed by in vitro proliferation assays. Overall, the single-cell transcriptomes of thousands of individual gamma delta T lymphocytes from different CMV+ and CMV- donors reflect cytotoxic maturation stages driven by the immunological history of donors. This landmark study establishes the rationale for identification, subtyping, and deep characterization of human gamma delta T lymphocytes in further scRNA-seq studies of complex tissues in physiological and disease conditions.

• Publisher: National Academy of Sciences,CCSD
• Subject: Adult / Base Sequence / Biological Sciences / Biotechnology / Blood / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / Cell proliferation / Cell Proliferation - physiology / Cells, Cultured / Clustering / Computer memory / Cytotoxicity / Datasets / Effector cells / Embedding / Gene expression / Gene sequencing / Human health and pathology / Humans / Immunologic Memory - immunology / Immunology / Immunology and Inflammation / Killer Cells, Natural - immunology / Leukocytes (mononuclear) / Leukocytes, Mononuclear - immunology / Life Sciences / Lymphocytes / Lymphocytes T / Maturation / Memory cells / Peripheral blood mononuclear cells / PNAS Plus / Receptors, Antigen, T-Cell, gamma-delta - immunology / Ribonucleic acid / RNA / Sequence Analysis, RNA - methods / T cell receptors / T-Lymphocyte Subsets - immunology / Transcriptome - immunology / Vertebrates
• ISBN: 0004710397000