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

Sarah C. Edwards, Caroline E. Sutton, Kristin Ladell, Emma J. Grant, James E. McLaren, Fiona Roche, Pradyot Dash, Nopporn Apiwattanakul, Walid Awad, Kelly L. Miners, Stephen J. Lalor, Julie C. Ribot, Song Baik, Barry Moran, Aoife McGinley, Valerie Pivorunas, Lori Dowding, Michael Macoritto, Jesus Paez-Cortez, Anthony SlavinGraham Anderson, Bruno Silva-Santos, Karsten Hokamp, David A. Price, Paul G. Thomas, Rachel M. McLoughlin, Kingston H.G. Mills

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Abstract

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.

Original languageEnglish
Article numbere20190834
Number of pages16
JournalJournal of Experimental Medicine
Volume217
Issue number5
DOIs
Publication statusPublished - 4 May 2020

Cite this

Edwards, S. C., Sutton, C. E., Ladell, K., Grant, E. J., McLaren, J. E., Roche, F., Dash, P., Apiwattanakul, N., Awad, W., Miners, K. L., Lalor, S. J., Ribot, J. C., Baik, S., Moran, B., McGinley, A., Pivorunas, V., Dowding, L., Macoritto, M., Paez-Cortez, J., ... Mills, K. 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]. https://doi.org/10.1084/jem.20190834