The proportion and phenotypic changes of CD4(+)CD25(−)Foxp3(+) T cells in patients with untreated rheumatoid arthritis

OBJECTIVE: CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell-mediated immunosuppression is an essential mechanism of rheumatoid arthritis (RA). However, little is known regarding the specific role of CD4(+)CD25(−)Foxp3(+) Treg cells in RA. This study aimed to investigate the frequency of circulating CD4(+)CD25(−)Foxp3(+) Treg cells and their role in RA. METHODS: Sixty-one untreated RA patients and 40 healthy controls (HCs) were enrolled in this study. The proportion of CD4(+)CD25(−)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) Tregs; the levels of CTLA4, GITR, Helios, and ICOS; and the production of IL-17A, IFN-γ, and IL-10 were assessed by flow cytometry. The correlation of CD4(+)CD25(–)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) Tregs with the clinical indicators was conducted by Spearman correlation analysis. RESULTS: The proportion of CD4(+)CD25(–)Foxp3(+) T cells was elevated in RA and positively correlated with disease activity. CD4(+)CD25(–)Foxp3(+) T cells expressed less Helios and produced more IFN-γ than conventional Tregs in RA. Additionally, the proportion of CD4(+)CD25(–)Foxp3(+) T cells was positively correlated with DAS28 score, IgG titer, and anti-CCP titer. CONCLUSIONS: These data indicate that CD4(+)CD25(−)Foxp3(+) T cells in RA exhibit several different functional properties from conventional Tregs and are correlated with RA disease activity.