调节性T细胞和辅助性T细胞17的平衡变化在慢性乙型肝炎病毒感染中的作用

目的 研究调节性T细胞(Treg)和辅助性T细胞17(Th17)的平衡变化在慢性HBV感染中的作用.方法 应用ELISA法和流式细胞术分别对34例慢性乙型肝炎(CHB)患者、20例HBV相关慢加急性肝功能衰竭(ACHBLF)患者和20例健康对照者外周血中Treg和Th17分化相关细胞因子及外周血Th17和Treg细胞水平进行检测.计数资料应用Fisher's确切概率法,计量资料应用单因素方差分析和Tukey's多重比较检验.结果 ACHBLF组Th17分化相关因子IL-1β为(3.97±2.85) pg/mL,IL-6为(12.75±8.87)pg/mL,IL-21为(360.0±335.7)pg/mL,比健康对照组的IL-1β(1.87±0.94)pg/mL,q=4.559,P＜0.01)、IL-6(5.28±o.72)pg/mL,q=7.309,P＜0.01)和IL-21(46.68±20.17) pg/mL,q=6.946,P＜0.01)均明显上调.ACHBLF组外周血Th17细胞比例明显高于健康对照组(q=3.972,P＜0.05).与健康对照组和ACHBLF组相比,CHB组Treg细胞分化相关因子TGF-β明显升高(q=4.536、5.323,均P＜0.01),外周血Treg比例也明显升高.ACHBLF组Th17细胞效应因子IL-17A水平最高,ACHBLF患者外周血Th17细胞比例与血清TBil水平呈正相关(γ=0.74,P＜0.01).结论 慢性HBV感染中,宿主免疫存在Th17和Treg失衡,ACHBLF组以Th17细胞活动为主,CHB组以Treg细胞活动为主.

Effects of T helper type 17 cells and T regulatory cells imbalance in patients with chronic hepatitis B virus infection

Objective To investigate the effects of the imbalance between regulatory T cells (Treg) and T helper 17 cells (Th17) in patients with chronic hepatitis B virus (HBV) infection.Methods The serum concentration of Treg/Th17 differentiation-related cytokines in 34 patients with chronic hepatitis B (CHB),20 patients with HBV related acute on chronic liver failure (ACHBLF),and 20 healthy controls (NC) were measured by enzyme-linked immunosorbent assay (ELISA) and proportion of peripheral Th17 and Treg cells were analyzed by flow cytometry.Numeration data was analyzed by Fisher's exact propability method and measurement data was tested by one-factor analysis of variance or Turkey multiple comparison.Results The levels of Th17 differentiation-related cytokines,II-1β (3.97±2.85) pg/mL,IL-6 (12.75±-8.87) pg/mL,and IL-21 (360.0±335.7) pg/ mL in patients with ACHBLF were significantly increased than those in NC,which were (1.87 ±0.94) pg/mL(q=4.559,P＜0.01),(5.28±0.72) pg/mL(q=7.309,P＜0.01) and (46.68±20.17) pg/mL(q=6.946,P＜0.01 ),respectively.The proportion of Th17 increased markedly in patients with ACHBLF than that in NC(q=3.972,P＜0.05).However,compared to NC and patients with ACHBLF,the Treg differentiation-related cytokine,TGF-β,in patients with CHB,increased significantly (q=4.536 and 5.323,respectively; both P＜0.01).And the population of Treg also increased markedly in CHB patients.The level of IL-17A which was the characteristic effector cytokine of Th17 was the highest in patients with ACHBLF.The peripheral Th17 cell proportion was positively correlated with the level of serum total bilirubin in patients with ACHBLF (γ=0.74,P＜0.01).Conclusions Th17 and Treg imbalance including cytokine profiles and cell numbers exists in patients with chronic HBV infection.The Th17 are active in patients with ACHBLF and Treg are active in patients with CHB.