The Changes of CD4+CD25+ Foxp3+Regulatory T Cells and TGF-β、IL-10 in Peripheral Blood of URSA Patients

Objective：The aim of this study is to reveal the significance of Treg cells in materno-fetal tolerance and pathogenesis of URSA.

Method：All subjects were recruited from the Department of Obstetrics and Gynecology of Sun Yat-sen Memorial Hospital in China between September 2013 and January 2015. URSA non-pregnant women 50 cases, URSA missed abortion patients 50 cases, normal non-pregnant women 25 cases and normal early pregnant women 25 cases. PBMCs were isolated from venous blood using Ficoll–Hypaque density centrifugation; The proportions of CD4⁺CD25⁺Treg cells inperipheral CD4⁺T cells were analyzed by flow cytometry, the expression of Foxp3 mRNA were analyzed by qRT-PCR, serum level of TGF-β and IL-10 were detected by ELISA.

Results: The proportions of Treg/CD4+T cells were significantly higher in normal pregnant women than in non-pregnant women （7.38±1.48 VS 5.67±0.94，P＜0.0001） and also higher in URSA missed abortion patients than in URSA non-pregnant women(5.72±1.00 VS 5.26± 1.08，P＝0.03). The proportions of Treg/CD4+T cells were significantly lower in URSA missed abortion patients than in normal controls (5.72±1.00 VS 7.38±1.48，P＜0.0001). The expression of Foxp3 mRNA were significantly higher in normal pregnant women than in non-pregnant women （3.43±0.46 VS 3.02±0.47，P=0.003） and also higher in URSA missed abortion patients than in URSA non-pregnant women(3.06±0.57 VS2.79±0.52，P＝0.01). The expression of Foxp3 mRNA were significantly lower in URSA missed abortion patients than in normal controls (3.06±0.57 VS3.43±0.46，P=0.006). Cytokines TGF-β and IL-10 were also lower in URSA patients than in normal controls（TGF-β：56.12±11.25 VS 50.12±9.78 ng/ml，P＝0.02；IL-10：6.43±2.48 VS 4.48±2.12 pg/ml，P＜0.001）.

Conclusion:Down-regulation of Treg cells during the first trimesterof pregnancy may involve in the pathogenesis of URSA.