Fig. 4

Identification of a population of pathogenic PD-1^HIGH KLRG1^LOW T cells in synovial fluid. Heatmap showing differential RNA expression levels of selected genes between PB and SF within the CD8 HLA-DR^HIGH T cells (A). Volcano plot showing genes that were up- or downregulated in SF HLA-DR^HIGH cells (B). UMAP plots show the enriched population of cells expressing the genes upregulated in SF CD8 HLA-DR^HIGH T cells, now compared to PB CD8 HLA-DR^HIGH T cells (C). Density plot comparing the distribution of the expression levels of KLRG1 in cytotoxic CD8 KLRG1^LOW cells from SF and PB (D). Volcano plot displaying up- or downregulated genes in SF cytotoxic CD8 KLRG1^LOW cells (E). UMAP plots show the enriched population of cells expressing the genes upregulated in SF cytotoxic CD8 KLRG1^LOW SF compared to PB (F). UMAP plot and density plot showing the populations and the spectrum of expression of KLRG1 in SF cytotoxic CD8 KLRG1^LOW and SF cytotoxic CD8 KLRG1^HIGH cells (G). Volcano plot displaying genes downregulated in cytotoxic CD8 KLRG1^HIGH cells and upregulated in cytotoxic CD8 KLRG1^LOW in SF (H). UMAP plots show the enriched population of cells expressing TIMP1 and ZNF683 in cytotoxic CD8 KLRG1^{LOW and} cytotoxic CD8 KLRG1^HIGH SF cells (I). Diagram showing the distinctive genes up- or downregulated in HLA-DR^HIGH KLRG1^LOW T cells from PB and SF (J). Violin plots summarizing the percentages of CD4⁺PD-1⁺KLRG⁺ T cells isolated from HC PB, RA PB, and RA SF samples and gated on N, CD, EM, and TEMRA subsets (Ki). Violin plots summarizing the percentages of CD8⁺PD-1⁺KLRG1⁺ T cell isolated from HC PB, RA PB, and RA SF samples and gated on N, CD, EM, and TEMRA subsets (Kii). Pearson correlation analysis between the percentages of CD8⁺PD-1⁺KLRG1.⁺ T cells and CRP (L) and DAS28 (M). Statistical significance was determined using ordinary 1-way ANOVA, post hoc test applying Šidák’s multiple comparisons; * p < 0.05, n = 5–30