自身免疫病患者外周血CD4^+CD25^+Foxp3^+调节性T细胞的表达和意义

Reduction and significance of CD4^+CD25^+Foxp3^+ T regulatory cells in the peripheral blood of patients with common autoimmune diseases

目的观察自身免疫病(AID)患者外周血CD4^+CD25^+Foxp3^+调节性T细胞的变化并探讨其意义。方法收集资料完整的AID患者1 561例及健康对照组196名,对外周血CD4^+CD25^+Foxp3^+调节性T细胞绝对计数及其与其他T细胞亚群[总T细胞、CD4^+ T细胞、T辅助细胞(Th)1、Th2、Th17、CD8^+T细胞的比值进行分析,并进行T细胞亚群与炎性指标的相关性分析。采用独立样本t检验、Mann-Whitney U检验、χ^2检验和Spearman相关性分析进行统计学分析。结果① AID组外周血调节性T细胞[22.9(18.31,36.47)与30.24(21.85,41.34),Z=-3.974,P<0.01]、总T细胞(Z=-4.234,P<0.01)、CD8^+T细胞(Z=-3.801,P<0.01)、Th17(Z=-3.740,P<0.01)细胞绝对计数水平低于健康对照组,CD4^+T细胞/调节性T细胞(Z=-3.366,P=0.001)、Th1/调节性T细胞(Z=-3.213,P=0.001)、Th2/调节性T细胞(Z=-2.490,P=0.013)水平高于健康对照组。② AID患者外周血T细胞亚群与ESR、CRP、补体C3、C4、病程等存在相关性。③复治患者调节性T细胞(Z=-3.624,P<0.01)、总T细胞(Z=-2.954,P=0.009)、CD4^+T细胞(Z=-3.005,P=0.003)、Th2(Z=-1.896,P=0.049)细胞绝对计数水平低于初治患者,总T细胞/调节性T细胞(Z=-2.460,P=0.014)、CD8+T细胞/调节性T细胞(Z=-3.197,P=0.001)水平高于初治患者。④脏器受累患者调节性T细胞(Z=-7.105,P<0.01)、总T细胞(Z=-4.892,P<0.01)、CD4+T细胞(Z=-6.909,P<0.01)、Th1(Z=-4.875,P<0.01)、Th2(Z=-5.751,P<0.01)、Th17(Z=-5.121,P<0.01)细胞绝对计数水平低于非脏器受累患者,总T细胞/调节性T细胞(Z=-4.500,P<0.01)、CD8^+T细胞/调节性T细胞(Z=-5.925,P<0.01)水平高于非脏器受累患者。⑤ AID患者T细胞亚群绝对计数水平与是否为单一AID和(或)为多种AID重叠无明显相关。结论AID患者外周血调节性T细胞水平明显下降,且与炎性指标存在相关性,复治患者较初治患者调节性T细胞进一步降低,脏器受累者调节性T细胞水平更低,表明调节性T细胞在AID的发病机制中可能起重要的作用。

Objective To determine the CD4^+CD25^+Foxp3^+ T regulatory (Treg) cell levels in peripheral blood (PB) of patients with autoimmune diseases (AID) and age-and sex-matched healthy controls. Methods Clinical data and laboratory examinations of AID cases (n=1 561) and healthy controls (n=196) were enrolled. The levels of PB Treg cells, other T lymphocyte subsets [total T, CD4^+ T, CD8+ T, T helper1 (Th1), T helper 2 (Th2), and T helper17(Th17) cells] and clinical indicators, laboratory test results were analyzed retro-spectively. Data were analyzed by t test, Mann-Whitney U test,χ^2 test and Spearman correlation analysis. Results ① The absolute counts of Treg [22.9(18.31, 36.47) vs 30.24(21.85, 41.34), Z=-3.974, P<0.01], total T (Z=-4.234, P<0.01), CD8+T (Z=-3.801, P<0.01), Th17 (Z=-3.740, P<0.01) cells in PB of patients with AID were significantly lower than those of healthy controls, the levels of CD4^+ T/Treg (Z=-3.366, P=0.001), Th1/Treg (Z=-3.213, P=0.001) and Th2/Treg (Z=-2.490, P=0.013) in PB of AID patients were higher than those of healthy controls.② The levels of inflammatory indicators were associated with numbers of T lymphocyte subsets.③ The levels of Treg (Z=-3.624, P<0.01), total T (Z=-2.954, P=0.009), CD4^+ T (Z=-3.005, P=0.003), Th2(Z=-1.896, P=0.049) cells in PB of the patients who had been treated with hormones and/or biological or non-biological disease-modifying anti-rheumatic drugs (DMARDs) were significantly lower while the levels of total T/Treg(Z=-2.460, P=0.014), CD8^+ T/Treg (Z=-3.197, P=0.001) in PB were higher than those of the primary treatment patients.④ The levels of Treg (Z=-7.105, P<0.01), total T (Z=-2.954, P<0.01), CD4^+ T (Z=-6.909, P<0.01), Th1 (Z=-4.875, P<0.01), Th2 (Z=-5.751, P<0.01), Th17 (Z=-5.121, P<0.01) cells in PB of the patients with important organs involvement were lower while the ratios of total T/Treg (Z=-4.500, P<0.01), CD8^+ T/Treg(Z=-5.925, P<0.01) were higher than those non-organ involvement patients.⑤ The absolute counts levels of T lymphocyte subsets in the AID patients were not significantly correlated with whether there was a single AID and/or multiple AID overlaps. Conclusion The absolute number of peripheral Treg cells decreases significantly in AID, and is correlated with inflammatory indicators. Patients with retreated and organ involve-ment have fewer Treg cells. Our results suggest that Treg cells may play an important role in the pathogenesis of AID.