Single-cell transcriptomes and T cell receptor sequences of memory T lymphocytes from the peripheral blood and the synovial fluid of patients with juvenile idiopathic arthritis.

Antigen-experienced (or memory) T lymphocytes were isolated from the synovial fluid of inflamed joints and the peripheral blood of patients with juvenile idiopathic arthritis (JIA). After flow-sort of CD4+CD45RO+CD25- (Tcon), CD4+CD45RO+CD127loCD25+ (Treg) and CD8+CD45RO+ T cells, single-cell RNA-sequencing was conducted to perform paired analyses of gene transcription and T cell receptor (TCR) repertoires in the same cells. The study aimed to identify T memory cells that were stimulated by antigens in inflamed joints of JIA patients and which perpetuate chronic inflammation by expression pro-inflammatory genes. In addition, the study aimed at understanding the clonal relationships of T cells differentiating at chronically inflamed sites, as well as to identify blood-circulating T cell clones that shared gene expression and antigen-specificity with T cells in inflamed joints in order to improve patient stratification and diagnostics of patients with chronic inflammatory diseases in the future. Single-cell RNA-sequencing and TCR immunoprofiling of flow-sorted CD4+CD45RO+CD25-, CD4+CD45RO+CD127loCD25+ and CD8+CD45RO+ T cells from paired blood and synovial fluid samples of patients with JIA were performed.