HBV感染患者外周血T细胞PD-1基因表达水平的变化与意义  

PD-1 expression in peripheral T cells of patients with HBV infection and its significance

作　　者：彭国平[1] 孙雯[2] 孙箴[1] 朱嘉珺[2] 李淑萍[1] 陈智[1] 

机构地区：[1]浙江大学医学院附属第一医院传染病研究所传染病诊治国家重点实验室,浙江杭州310003 [2]浙江大学医学院附属口腔医院,浙江杭州310031

出　　处：《浙江大学学报（医学版）》2007年第6期553-560,共8页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(30471537)

摘　　要：目的:分析HBV感染不同阶段患者外周血T淋巴细胞中PD-1(program death factor-1)分子的基因定量表达情况,探讨PD-1表达水平与血清学指标的相关性。方法:采集并筛选HLA-A2阳性的31例慢性乙型肝炎(CHB)患者、9例急性恢复期乙型肝炎患者(AHB)、15例乙肝相关性肝硬化患者(LC)和10例健康献血者的外周血,实时荧光定量PCR分析总T细胞内PD-1的mRNA水平,同时测定其配体PD-L1、PD-L2在外周血单个核细胞(PBMCs)中的表达量;酶联免疫吸附试验(ELISA)检测HBV血清标记物水平,荧光定量PCR检测血清HBV DNA载量,同时进行肝功能检测。结果:以各基因在正常对照组的定量表达水平为基础值,HBeAg阳性CHB组T细胞内PD-1和PBMCs内PD-L1的mRNA表达水平明显升高,与HBeAg阴性CHB组和AHB组比较均有显著性差异,但与LC组比较无统计学意义(P>0.05)。外周血PBMCs内PD-L2的mRNA水平在各实验组中无明显差异(P均>0.05)。在所有检测的CHB患者中,外周血T细胞内PD-1表达水平在高病毒载量组(HBV DNA≥107拷贝/ml)明显高于低病毒载量组(HBV DNA<107拷贝/ml)和正常对照组,且与血清HBV病毒载量成正相关(r=0.41,P<0.01),但与血清ALT水平无明显相关性。结论:外周血T细胞中PD-1基因水平在慢性乙型肝炎患者组,尤其是在HBeAg阳性组和高病毒载量组明显上调,提示T细胞高表达的PD-1可能通过与其配体PD-L1作用而抑制T细胞免疫应答,并导致病毒持续感染。Objective： To analyze the expression levels of PD-1 （program death factor-1）in peripheral T cells from patients infected with HBV,and tO investigate its relationship with HBV serological markers. Methods： A total of 65 HLA-A2 ＋ subjects,including 31 patients with chronic hepatitis B （CHB）,9 with acute resolved hepatitis B （AHB）, 15 with HBV related liver cirrhosis （LC） and 10 healthy blood donators,were enrolled. The expression of PD-1 in peripheral T cells and PD-1 ligands PD-L1 and PD-L2 in PBMCs were determined by relative quantitative real-time PCR. The serum HBV markers,HBV DNA load and liver function were also measured. Results： Taken the PD-1 and PD-ligands expression in normal controls as a baseline level,the expression of PD-1 and PD-L1 from CHB patients was significantly increased, while the expression of PD-L2 was relatively low in all groups. In CHB patients,the PD-1 expression in peripheral T cells from patients with high viral load was much higher than that from those with low viral load or from normal controls. And the PD-1 expression level positively correlated with serum HBV DNA load （r=0.41,P〈0. 01） but not with serum ALT level. Conclusion： Long -term exposure to HBV antigens in CHB patients may increase the expression of PD-1 in T cells and thus leads to the virus persistent infection.

关 键 词：肝炎 乙型 慢性/免疫学 T淋巴细胞 免疫抑制 病毒载量 

分 类 号：R512.6[医药卫生—内科学]