Transcriptional profiling of human Vδ1 T cells reveals a pathogen-driven adaptive differentiation program.

Autor: McMurray JL; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., von Borstel A; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Taher TE; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Syrimi E; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK; Department of Haematology, Birmingham Children's Hospital, Birmingham B4 6NH, UK., Taylor GS; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Sharif M; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Rossjohn J; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia., Remmerswaal EBM; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Bemelman FJ; Renal Transplant Unit, Division of Internal Medicine, Academic Medical Centre, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Vieira Braga FA; Wellcome Sanger Institute, Cambridge, UK., Chen X; Wellcome Sanger Institute, Cambridge, UK., Teichmann SA; Wellcome Sanger Institute, Cambridge, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge CB10 1SD, UK., Mohammed F; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Berry AA; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA., Lyke KE; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA., Williamson KC; Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Stubbington MJT; Wellcome Sanger Institute, Cambridge, UK., Davey MS; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. Electronic address: martin.davey@monash.edu., Willcox CR; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK. Electronic address: c.r.willcox@bham.ac.uk., Willcox BE; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK. Electronic address: b.willcox@bham.ac.uk.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2022 May 24; Vol. 39 (8), pp. 110858.
DOI: 10.1016/j.celrep.2022.110858
Abstrakt: γδ T cells are generally considered innate-like lymphocytes, however, an "adaptive-like" γδ compartment has now emerged. To understand transcriptional regulation of adaptive γδ T cell immunobiology, we combined single-cell transcriptomics, T cell receptor (TCR)-clonotype assignment, ATAC-seq, and immunophenotyping. We show that adult Vδ1 + T cells segregate into TCF7 + LEF1 + Granzyme B neg (T naive ) or T-bet + Eomes + BLIMP-1 + Granzyme B + (T effector ) transcriptional subtypes, with clonotypically expanded TCRs detected exclusively in T effector cells. Transcriptional reprogramming mirrors changes within CD8 + αβ T cells following antigen-specific maturation and involves chromatin remodeling, enhancing cytokine production and cytotoxicity. Consistent with this, in vitro TCR engagement induces comparable BLIMP-1, Eomes, and T-bet expression in naive Vδ1 + and CD8 + T cells. Finally, both human cytomegalovirus and Plasmodium falciparum infection in vivo drive adaptive Vδ1 T cell differentiation from T naive to T effector transcriptional status, alongside clonotypic expansion. Contrastingly, semi-invariant Vγ9 + Vδ2 + T cells exhibit a distinct "innate-effector" transcriptional program established by early childhood. In summary, adaptive-like γδ subsets undergo a pathogen-driven differentiation process analogous to conventional CD8 + T cells.
Competing Interests: Declaration of interests M.J.T.S. has been employed by 10× Genomics since April 2018; this employment had no bearing on this work. The other authors declare no competing financial interests.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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