A population of proinflammatory T cells coexpresses ?? and ?? T cell receptors in mice and humans.

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

SUBMITTER: Edwards SC 

PROVIDER: S-EPMC7201916 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature