Pediatric rheumatology

Single-cell profiling reveals CCL5Hi GZMAHi effector memory CD8 T cell association to oligoarticular JIA

Rheumatology (Oxford)Published Mechanistic study

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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