Single-cell profiling reveals CCL5Hi GZMAHi effector memory CD8 T cell association to oligoarticular JIA
Authors' conclusion
Clonally expanded, cytotoxic CD8+ TEM cells drive joint inflammation in oligo JIA, while activated MAIT and NK cells in uveitis indicate systemic immune activation and potential therapeutic targets.
Study context
- Population
- Patients with oligoarticular JIA, with and without uveitis flare, and age-matched healthy controlsdiscovery cohort
- Comparison
- Oligo JIA and oligo JIA with uveitis flare vs age-matched healthy controls (HCs)
- New-onset oligo JIAn = three
- Uveitis flaren = four
- HCsn = fourreference
- Outcome
- Immune landscape of oligo JIA (scRNA-seq of 132 824 immune cells)
Methodological detailssingle-cell RNA and TCR sequencing, independent validation cohort (CyTOF)
- Single-cell RNA and TCR sequencing
- Independent validation cohort (CyTOF)
Main finding
As reported in the abstract
- Enrichment of activated CD8+TEM, intermediate monocytes and regulatory T cells in SF
- CD8+TEM depleted in blood, suggesting recruitment from the circulation into the inflamed joint
- SF CD8+TEM: upregulation of CCL5, GZMA and GNLY and marked clonal expansion
- Uveitis: MAIT cells clonally expanded and transcriptionally reprogrammed with IFN-stimulated and cytotoxic signatures
Further findings
Validation by CyTOF (13 oligo JIA, eight uveitis flare, six HCs)
- Reduced circulating CCL5Hi GZMAHi CD8+TEM in oligo JIA
- Independent cohort
Original publication
Single-cell profiling reveals CCL5Hi GZMAHi effector memory CD8 T cell association to oligoarticular JIA. Rheumatology (Oxford). Published 27 April 2026. doi:10. 1093/ rheumatology/ keag211
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