Altered frequency and migration capacity of CD4+CD25+ regulatory T cells in systemic lupus erythematosus

Abstract

OBJECTIVES: To determine the frequency and chemokine receptor-related migratory capacity of CD4(+)CD25(+) regulatory T cells (Tregs) and their association with clinical parameters in patients with SLE. METHODS: The expression of CD4, CD25, FoxP3 and CCR4 was examined with flow cytometry after staining with fluorescence-conjugated antibodies in 20 patients with SLE, 20 patients with RA and 21 age- and sex-matched healthy controls. For analysis of migration capacity in 24-well chemotaxis chambers, sorted cells were stimulated with ligands of CCR4, CCL17 and CCL22 and analysed with FACScan. Correlations between the number of Tregs and CCR4(+) Treg cells and clinical parameters were analysed. RESULTS: The numbers of Tregs(bright) and CCR4(+) Tregs(bright) were significantly decreased in the patients with SLE compared with healthy controls. The number of Tregs(bright) was negatively correlated with the levels of anti-dsDNA antibody and the number of CCR4(+) Tregs(bright) had a positive correlation with the levels of C(3). Percentage of migrated Tregs(bright) by CCL17 or CCL22 was significantly decreased in the patients with SLE compared with healthy controls. CONCLUSIONS: These results suggest that altered frequency of Tregs and CCR4(+) Tregs(bright) and decreased migratory capacity of Tregs might be involved in the pathogenesis of SLE and indicate that targeting the Tregs can be a new therapeutic strategy in SLE.