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

McMurray, Jack L., von Borstel, Anouk, Taher, Taher E., Syrimi, Eleni, Taylor, Graham S., Sharif, Maria, Rossjohn, Jamie ORCID:, Remmerswaal, Ester B.M., Bemelman, Frederike J., Vieira Braga, Felipe A., Chen, Xi, Teichmann, Sarah A., Mohammed, Fiyaz, Berry, Andrea A., Lyke, Kirsten E., Williamson, Kim C., Stubbington, Michael J.T., Davey, Martin S., Willcox, Carrie R. and Willcox, Benjamin E. 2022. Transcriptional profiling of human Vδ1 T cells reveals a pathogen-driven adaptive differentiation program. Cell Reports 39 (8) , 110858. 10.1016/j.celrep.2022.110858

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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 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This is an open access article under the terms of the CC-BY Attribution 4.0 International license.
Publisher: Cell Press
ISSN: 2211-1247
Date of First Compliant Deposit: 25 July 2022
Date of Acceptance: 2 May 2022
Last Modified: 07 May 2023 07:07

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