A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans
Year: 2020
Type: article
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.
DOI: 10.1084/jem.20190834
Authors: 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 Slavin, Graham Anderson, Bruno Silva-Santos, Karsten Hokamp, David A. Price, Paul G. Thomas, Rachel M. McLoughlin, Kingston H.G. Mills
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Funders: AbbVie, Wellcome Trust, American Lebanese Syrian Associated Charities, Higher Education Authority, Science Foundation Ireland, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Institute of Allergy and Infectious Diseases, H2020 European Research Council
Awards: Biomarkers and drug targets for autoimmune diseases, Profiling immune signatures predictive of outcome in Staphylococcus aureus infection: Advancing next generation vaccine design, G3204348948, The immunopathogenesis of Epstein-Barr virus-associated malignancies., Understanding the role of T cells in sustained protective immunity to Bordetella pertussis to inform the design of third generation vaccines against pertussis, Flow Cytometry Cell Sorter, New immunotherapeutic approaches based on the Th1/Th17 axis and its regulation, Mechanisms to diversify repertoire and modify T cell activity after infection, G8154560156, G8173526563
OpenAlex ID: W3007464489