A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans
| Autor: | Jesus Paez-Cortez, Paul G. Thomas, Song Baik, David Price, Karsten Hokamp, Sarah C. Edwards, Bruno Silva-Santos, Rachel M. McLoughlin, Stephen J. Lalor, Valerie Pivorunas, Caroline E. Sutton, Graham Anderson, Walid Awad, Barry Moran, Julie C. Ribot, James E. McLaren, Aoife M. McGinley, Anthony Slavin, Fiona M. Roche, Pradyot Dash, Kristin Ladell, Nopporn Apiwattanakul, Kingston H. G. Mills, Michael Macoritto, Kelly L. Miners, Lori Dowding, Emma J. Grant |
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| Rok vydání: | 2020 |
| Předmět: |
Staphylococcus aureus
Encephalomyelitis Autoimmune Experimental Transcription Genetic Receptors Antigen T-Cell alpha-beta T-Lymphocytes T cell Immunology Population Autoimmunity Biology Lymphocyte Activation 03 medical and health sciences Chemokine receptor 0302 clinical medicine Neuroinflammation Antigen medicine Animals Humans Immunology and Allergy education 030304 developmental biology Inflammation 0303 health sciences education.field_of_study T-cell receptor Brief Definitive Report Receptors Antigen T-Cell gamma-delta Staphylococcal Infections 3. Good health Cell biology Mice Inbred C57BL Phenotype medicine.anatomical_structure Interleukin 17 Transcriptome Biomarkers CD8 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20190834 |
| Popis: | T cells classically express either αβ or γδ T cell receptors. We have identified T cells that express both pairs of receptors. These hybrid αβ-γδ T cells exhibit a hyperinflammatory and migratory phenotype and act as first responders in infection and CNS autoimmunity. 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. Graphical Abstract |
| Databáze: | OpenAIRE |
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