Sarah C. EdwardsCaroline E. SuttonKristin LadellEmma J. GrantJames E. McLarenFiona RochePradyot DashNopporn ApiwattanakulWalid AwadKelly L. MinersStephen J. LalorJulie C. RibotSong BaikBarry MoranAoife McGinleyValerie PivorunasLori DowdingMichael MacorittoJesus Paez-CortezAnthony SlavinGraham AndersonBruno Silva-SantosKarsten HokampDavid A. PricePaul G. ThomasRachel M. McLoughlinKingston H.G. MillsAbbVieCardiff UniversityUniversity of Lisbon Faculty of Medicine, Institute of Molecular MedicineSt. Jude Children's Research HospitalUniversity of BirminghamMonash UniversityFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityTrinity College Dublin2020-03-262020-03-262020-05-04The Journal of experimental medicine. Vol.217, No.5 (2020)154095382-s2.0-85081563962https://repository.li.mahidol.ac.th/handle/20.500.14594/53686© 2020 Edwards et al. 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.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1084/jem.20190834