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

Edwards, Sutton, Ladell, Grant, McLaren, Roche, Dash, Apiwattanakul, Awad, Miners, Lalor, Ribot, Baik, Moran, McGinley, Pivorunas, Dowding, Macoritto, Paez-Cortez, Slavin, Anderson, Silva-Santos, Hokamp, Price, Thomas, McLoughlin, Mills (2020) A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans J Exp Med (IF: 15.3) 217(5)

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.© 2020 Edwards et al.

Links

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201916
http://www.ncbi.nlm.nih.gov/pubmed/32106283
http://dx.doi.org/10.1084/jem.20190834

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