Inverse correlation between CD4+ regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus

CD4(+) CD25(+) regulatory T cells (Tregs) are critical in maintaining self-tolerance and preventing organ-specific autoimmunity. Their role in paediatric systemic lupus erythematosus (SLE), an autoimmune disease characterized by inappropriate regulation of hyperactivated B and T cells, has not been clearly defined. Using flow cytometry to determine cell populations and real-time polymerase chain reaction to assay mRNA expression for FOXP3, CTLA-4, and GITR, we characterized CD4(+) CD25(+) T cells in paediatric SLE patients and healthy subjects. The frequency of CD4(+) CD25(+) Tregs was significantly decreased in patients with active SLE compared with patients with inactive SLE and with controls (7.27% +/- 2.50%, 9.59% +/- 2.80% and 9.78% +/- 2.11%, respectively; P = 0.027 and P < 0.001, respectively), and was inversely correlated with disease activity, as assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 scores (r = -0.59, P = 0.001) and serum anti-double-stranded DNA levels (r = -0.65, P < 0.001). Our preliminary investigations found elevated surface expression of GITR in CD4(+) CD25(+) T cells, elevated mRNA expression of CTLA-4 in CD4(+) T cells and higher amounts of mRNA expression for FOXP3 in CD4(+) cells in patients with active SLE compared with patients with inactive disease and controls. We demonstrated reduced CD4(+) CD25(+) Treg levels were inversely correlated with disease activity, indicating a defective Treg population in paediatric SLE patients. The differences in the expression of FOXP3, CTLA-4 and GITR imply the possible role of CD4(+) Tregs in the pathogenesis of SLE.