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A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans

Edwards, Sarah C., Sutton, Caroline E., Ladell, Kristin ORCID:, Grant, Emma J., McLaren, James E. ORCID:, Roche, Fiona, Dash, Pradyot, Apiwattanakul, Nopporn, Awad, Walid, Miners, Kelly L., Lalor, Stephen J., Ribot, Julie C., Baik, Song, Moran, Barry, McGinley, Aoife, Pivorunas, Valerie, Dowding, Lori, Macoritto, Michael, Paez-Cortez, Jesus, Slavin, Anthony, Anderson, Graham, Silva-Santos, Bruno, Hokamp, Karsten, Price, David A. ORCID:, Thomas, Paul G., McLoughlin, Rachel M. and Mills, Kingston H.G. 2020. A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans. Journal of Experimental Medicine 217 (5) , e20190834. 10.1084/jem.20190834

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T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR–mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. Hybrid αβ-γδ T cells were transcriptomically distinct from conventional γδ T cells and displayed a hyperinflammatory phenotype enriched for chemokine receptors and homing molecules that facilitate migration to sites of inflammation. These proinflammatory T cells promoted bacterial clearance after infection with Staphylococcus aureus and, by licensing encephalitogenic Th17 cells, played a key role in the development of autoimmune disease in the central nervous system.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Rockefeller University Press
ISSN: 0022-1007
Date of First Compliant Deposit: 12 March 2020
Date of Acceptance: 17 January 2020
Last Modified: 03 May 2023 10:45

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