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

T cells are classically recognized as distinct subsets that express alphabeta or gammadelta TCRs. We identify a novel population of T cells that coexpress alphabeta and gammadelta TCRs in mice and humans. These hybrid alphabeta-gammadelta T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent alphabeta TCR-mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRdelta+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-gamma, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1beta and IL-23. Hybrid alphabeta-gammadelta T cells were transcriptomically distinct from conventional gammadelta 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.