吲哚胺2，3-二氧化酶对乙肝患者T细胞的免疫抑制作用

Immunosuppressive effect of indoleamine 2,3-dioxygenase on T cells in patients with chronic hepatitis B

目的观察吲哚胺2,3-二氧化酶(IDO)在慢性乙型肝炎(乙肝)病毒感染方面的免疫耐受作用,从而为重建人体主动免疫提供一种新方法。方法采集50例慢性乙肝患者外周静脉血作为乙肝组,检测其乙肝病毒复制水平,T细胞亚群功能,以及IDOmRNA,蛋白定量以及表达活性。统计分析乙肝病毒(HBV)复制水平、T细胞亚群功能以及IDO表达三者之间的关系。采集50例健康体检人群外周静脉血作为正常对照组,以同样方法处理之。结果乙肝患者IDOmRNA、IDO蛋白定量、IDO表达活性均明显高于健康体检人群[mRNA:(2.110±0.615)×103vs(0.143±0.026)×103;蛋白定量:0.22±0.06vs0.02±0.0017;表达活性:26.07±8.12vs4.98±1.65;P<0.05],IDOmRNA与HBV(r=0.502,P<0.001)和ALT(r=0.65,P<0.01)均呈正相关。另外,IDOmRNA、蛋白定量和表达活性均与CD4(+)T细胞(r=-0.622,-0.682,-0.549,P<0.05)、CD8(+)T细胞(r=-0.487,-367,-294,P<0.05)以及CD4/CD8比值(r=-0.426,-0.533,-0.397,P<0.05)呈负相关。结论IDO与HBV密切相关,并且参与HBV的免疫耐受,抑制IDO的功能可以为打破乙肝病毒的免疫耐受提供一个新方法。

Objective To investigate the role of indoleamine 2;3-dioxygenase （IDO） in immune tolerance in patients with chronic hepatitis B （CHB）. Methods Peripheral venous blood samples were collected from 50 CHB patients, and HBV viral load, T lymphocyte subsets and oflDO mRNA, protein and activity were detected with the blood samples from 50 healthy donors as the control. The correlations between HBV viral load, T lymphocyte subsets and IDO were statistically analyzed. Result In CHB patients, the mRNA and protein levels and activity of IDO were all significantly higher than those in control group [mRNA： （2.110±0.615）×10^3 vs （0.143±0.026）×10^3; protein： 0.22±0.06 vs 0.02±0.0017; activity： 26.07±8.12 vs 4.98±1.65; P〈0.05 ]. IDO mRNA level was positively correlated to HBV viral load （r=0.502, P〈0.001） and ALT （r=0.65, P〈0.01）, and IDO mRNA, protein and activity were inversely correlated to CD4^＋ T cells （r=-0.622, -0.682, and -0.549, respectively, P〈0.05）, CD8^＋ T cells （r=-0.487, -367, and -294, respectively, P〈0.05） and the ratio of CD4/CD8 （r=-0.426, -0.533, and -0.397, respectively, P〈0.05）. Conclusion IDO is closely correlated to HBV viral load and responsible for immunotolerance against HBV. Suppression oflDO can be a new therapeutic approach to reverse immunotolerance in CHB.