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Cytotoxic CD8+ T cells target citrullinated antigens in rheumatoid arthritis.
- Source :
- Nature Communications; 1/19/2023, Vol. 14 Issue 1, p1-15, 15p
- Publication Year :
- 2023
-
Abstract
- The immune mechanisms that mediate synovitis and joint destruction in rheumatoid arthritis (RA) remain poorly defined. Although increased levels of CD8<superscript>+</superscript> T cells have been described in RA, their function in pathogenesis remains unclear. Here we perform single cell transcriptome and T cell receptor (TCR) sequencing of CD8<superscript>+</superscript> T cells derived from anti-citrullinated protein antibodies (ACPA)+ RA blood. We identify GZMB<superscript>+</superscript>CD8<superscript>+</superscript> subpopulations containing large clonal lineage expansions that express cytotoxic and tissue homing transcriptional programs, while a GZMK<superscript>+</superscript>CD8<superscript>+</superscript> memory subpopulation comprises smaller clonal expansions that express effector T cell transcriptional programs. We demonstrate RA citrullinated autoantigens presented by MHC class I activate RA blood-derived GZMB<superscript>+</superscript>CD8<superscript>+</superscript> T cells to expand, express cytotoxic mediators, and mediate killing of target cells. We also demonstrate that these clonally expanded GZMB<superscript>+</superscript>CD8<superscript>+</superscript> cells are present in RA synovium. These findings suggest that cytotoxic CD8<superscript>+</superscript> T cells targeting citrullinated antigens contribute to synovitis and joint tissue destruction in ACPA+ RA. The immune mechanisms underlying synovitis and joint tissue destruction in rheumatoid arthritis (RA) remain incompletely defined. Here, the authors demonstrate that ACPA+ RA patients have activated clonally expanded cytotoxic GZMB+ CD8+ T cells in blood and synovium that target and are activated by citrullinated antigens to mediate cell killing. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 14
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 161396710
- Full Text :
- https://doi.org/10.1038/s41467-022-35264-8