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dc.contributor.authorMcMurray, Jack L
dc.contributor.authorvon Borstel, Anouk
dc.contributor.authorTaher, Taher E
dc.contributor.authorSyrimi, Eleni
dc.contributor.authorTaylor, Graham S
dc.contributor.authorSharif, Maria
dc.contributor.authorRossjohn, Jamie
dc.contributor.authorRemmerswaal, Ester B M
dc.contributor.authorBemelman, Frederike J
dc.contributor.authorVieira Braga, Felipe A
dc.contributor.authorChen, Xi
dc.contributor.authorTeichmann, Sarah A
dc.contributor.authorMohammed, Fiyaz
dc.contributor.authorBerry, Andrea A
dc.contributor.authorLyke, Kirsten E
dc.contributor.authorWilliamson, Kim C
dc.contributor.authorStubbington, Michael J T
dc.contributor.authorDavey, Martin S
dc.contributor.authorWillcox, Carrie R
dc.contributor.authorWillcox, Benjamin E
dc.date.accessioned2022-06-02T14:16:21Z
dc.date.available2022-06-02T14:16:21Z
dc.date.issued2022-05-24
dc.identifier.urihttp://hdl.handle.net/10713/19052
dc.description.abstractγδ 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 Bneg (Tnaive) or T-bet+Eomes+BLIMP-1+Granzyme B+ (Teffector) transcriptional subtypes, with clonotypically expanded TCRs detected exclusively in Teffector 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 Tnaive to Teffector 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.en_US
dc.description.urihttps://doi.org/10.1016/j.celrep.2022.110858en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relationRaw data utilised in this study has been uploaded to the SRA database, under the accession code PRJNA562324 and the project title “Epigentic and transcriptional profiling of human gamma delta T cells”.en_US
dc.relation.ispartofCell Reportsen_US
dc.rightsCopyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.en_US
dc.subjectCP: Immunologyen_US
dc.subjectCP: Microbiologyen_US
dc.subjectT cell receptoren_US
dc.subjectadaptiveen_US
dc.subjectclonal expansionen_US
dc.subjectdifferentiationen_US
dc.subjecteffectoren_US
dc.subjectnaiveen_US
dc.subjectpathogenen_US
dc.subjecttranscription factoren_US
dc.titleTranscriptional profiling of human Vδ1 T cells reveals a pathogen-driven adaptive differentiation program.en_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.celrep.2022.110858
dc.identifier.pmid35613583
dc.source.journaltitleCell reports
dc.source.volume39
dc.source.issue8
dc.source.beginpage110858
dc.source.endpage
dc.source.countryUnited States


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