The expression and significance of CD4+CD25+ regulatory T cells in the peripheral blood of patients with systemic sclerosis

Abstract

Objective To study the phenotype and function of CD4+CD25+ Treg cells in the peripheral blood of patients with systemic sclerosis (SSc) and their relationship with fibrosis. Methods The proportion of Foxp3, CD127, CTLA-4 and CD69 on CD4+CD25+ Treg cells in peripheral blood were detect by flow cytometry; the levels of TGF-β1 and IL-10 in serum were detect by enzyme-linked immunosorbent assay (ELISA) in patients with SSc. The correlation between Treg cells and the score of chest HRCT, MRSS, and disease activity was analyzed. T test and Pearson correlation analysis were used for statistical analysis. Results ① Compare to the control group, the proportion of CD4+CD25+ Treg cells in peripheral blood of SSc patients was increased significantly (12.9±2.4 vs 14.9±2.2, t=2.63, P=0.012) , and the expression of CD69+, CTLA-4+ on CD4+CD25+ Treg cells was decreased significantly (P<0.01). ② Compare to the control group, the proportion of CD4+CD25+Foxp3+ cells and CD4+CD25+CD127- cells in peripheral blood of SSc patients was increased significantly (respectively, 3.3±0.7 vs 5.0±0.7, 5.1±1.6 vs 7.6±2.0, t=7.03, 4.195; P<0.01), but no correlation between them was detected. ③ The level of TGF-β1 in the serum of the SSc patients was lower than that of the control group (86±29 vs 133±29 ng/ml, t=-5.026, P=0.000). However, IL-10 had no significant difference between the two groups. ④ The proportion of CD4+CD25+Foxp3+ cells and CD4+CD25+CD127- cells in peripheral blood of SSc patients was positively correlated with the scores of chest HRCT (respectively, r=0.541, P=0.02; r=0.486, P=0.041), and no correlation was observed with ESR, CRP. In addition, CD4+CD25+Foxp3+ cells were associated with MRSS. Conclusion The proportion of CD4+CD25+ Treg cells in the peripheral blood of SSc patients is increased, but they alters the immune function. The different phenotypes of Treg cells of CD4+CD25+Foxp3+ cells and CD4+CD25+CD127- cells in peripheral blood of SSc patients are increased significantly, which changes along with skin and lung fibrosis. The associated cytokine TGF-β1 is reduced, and IL-10 is not significantly changed. Key words: Scleroderma, systemic; Transforming growth factor beta; CD4+CD25+ Treg cells; Foxp3; CD127- cells