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

Abstract

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.