Elevated circulating CD4 + ICOS + Foxp3 + T cells contribute to overproduction of IL-10 and are correlated with disease severity in patients with systemic lupus erythematosus

Abstract

In this work, we aimed to investigate the frequency, possible categories and clinical significance of circulating CD4⁺ICOS⁺FoxP3⁺ T cells in patients with systemic lupus erythematosus (SLE). The frequency of circulating CD4⁺ICOS⁺FoxP3⁺ T cells was analysed by flow-cytometric analysis in 32 SLE patients, 10 rheumatoid arthritis patients and 32 healthy controls. Production of IL-10 and mTGF-β by different CD4⁺ T-cell populations was determined by intracellular cytokine staining. Plasma levels of IL-10 and TGF-β were determined by enzyme-linked immunosorbent assay (ELISA). The frequency of circulating CD4⁺ICOS⁺FoxP3⁺ T cells was significantly increased in SLE patients as compared with control groups. The elevated frequency of CD4⁺ICOS⁺FoxP3⁺ T cells had a positive correlation with SLE Disease Activity Index (SLEDAI) scores and serum anti-dsDNA but a negative correlation with serum C3. Additionally, the CD4⁺ICOS⁺Foxp3⁺ T cells contained significantly higher percentages of IL-10-producing cells than CD4⁺ICOS⁻Foxp3⁺ T cells. A significant positive correlation was also observed between the frequency of CD4⁺ICOS⁺Foxp3⁺ T cells and the plasma level of IL-10 in SLE patients. In conclusion, an increased frequency of circulating CD4⁺ICOS⁺Foxp3⁺ T cells was observed in patients with SLE, suggesting its potential importance in the immunopathogenesis of SLE. Analysis of the CD4⁺ICOS⁺FoxP3⁺ T-cell population may be useful for the evaluation of lupus disease severity.