干扰素α对慢性丙型肝炎患者外周血T淋巴细胞表面程序性死亡受体-1表达的影响  

Dynamic changes in programmed death-1 expression on the surface of T cells in chronic hepatitis C patients undergoing interferon therapy

作　　者：董荣乔[1] 周东方[1] 韩冉[1] 周俊英[1] 赵彩彦[1] 甄真[1] 

机构地区：[1]河北医科大学第三医院感染科,石家庄050051

出　　处：《中华肝脏病杂志》2013年第12期899-902,共4页Chinese Journal of Hepatology

基　　金：河北省卫生厅科技攻关项目（20110443）

摘　　要：目的观察慢性丙型肝炎（CHC）患者用聚乙二醇干扰素α-2a（Peg—IFNα-2a）抗病毒治疗过程中T淋巴细胞亚群变化及其表面程序性死亡受体-1（PD-1）的表达情况。方法收集25例HCV基因1b型用Peg-IFNα-2a联合利巴韦林标准治疗方案抗病毒治疗获得快速病毒学应答的CHC患者和10例健康对照者资料，于抗病毒治疗的第0、4、12、24、48周用流式细胞术检测外周血CD4＋T淋巴细胞和CD8＋T淋巴细胞及其表面的PD-1的表达情况。用RT-PCR的方法检测外周血单个核细胞PD-1mRNA的表达情况，两组问均数比较用两独立样本的t检验，各组间比较用重复测量数据方差分析，相关性分析用Pearson相关分析。结果Peg—IFN α-2a联合利巴韦林抗病毒治疗过程中CD4＋T淋巴细胞、CD8＋T淋巴细胞以及CD4＋／CD8＋逐渐升高，各组比较，F值分别为81．23、39．28和7．01，P值均〈0．01，差异均有统计学意义。于0、4、12、24、48周时，CD4＋T淋巴细胞上PD-1的表达频率分别为9．03％±1．3％、6．91％±0．85％、6．80％±0．86％、5．18％±0．54％和3．89％±0．94％，各组比较，F=100．11，P〈0．01，差异有统计学意义;CD8＋T淋巴细胞上PD-1的表达频率分别为5．400／0±0．98％、4．23％±0．7％、3．08％±0．57％、2．05％±0．47％和1．35％±0．37％，各组比较，F=158．40，P〈0．01，差异有统计学意义；外周血单个核细胞上PD-1mRNA表达水平分别为1．40±0．26、1．30±0．27、1．14±＋0．18、1．06±0．26和0．83±0．25，各组比较，F=20．09，P〈0．01，差异有统计学意义。相关性分析结果显示基线水平CD4＋T和CD8＋T淋巴细胞PD-1表达频率与HCVRNA载量呈正相关（r值分别为0．82和0．75，尸值均〈0．01）。结论Peg—IFNα-2a抗HCV治疗机制可能与抑制CD4＋T淋巴细胞和CD8＋T淋巴细胞表面PD-1的表达有关。Objective To investigate the dynamic changes that occur in T cell subsets, particularly involving the surface expression of programmed death 1 （PD-1）, in response to pegylated （Peg）-interferon （IFN） α-2a therapy in patients with chronic hepatitis C virus （HCV） infection. Methods Twenty-five patients with HCV genotype lb chronic infection and 10 healthy controls were enrolled in the study. All the HCV patients received combination antiviral therapy of Peg-IFNα-2a （180 μg/week） plus ribavirin. At treatment weeks 0 （baseline）, 4, 12, 24 and 48, the level of PD-1 protein expression on the surface of total peripheral CD8＋ and CD4＋ T cells was determined by flow cytometry and thelevel of PD-1 mRNA expression in peripheral blood mononuclear cells （PBMCs） was determined by reverse transcription-polymerase chain reaction. Independent student＇s t-test were used to compare mean values between the two groups, repeat measure variance analysis was used to compare mean values among multiple groups, and Pearson＇s correlation coefficient was used to assess correlation significance. Results Over the course of antiviral therapy, the proportions of CD4＋ T cells and CD8＋ T cells, as well as the CD4＋/CD8＋ ratio, increased （F = 81.23, 39.28, and 7.01 respectively; all P 〈 0.01）. In contrast, the PD-1 protein expression frequency on CD4＋ T cells and CD8＋ T cells significantly declined （F = 100.11 and 158.40 respectively; allP 〈 0.01）. The PD- 1-mRNA expression level in PBMCs was： 1.40 ± 0.26 at baseline, 1.30 ± 0.27 at week-4, 1.14±0.18 at week-12, 1.06 ±0.26 at week-24, and 0.83 ± 0.25 at week- 48 （F = 20.09; P 〈 0.01）. A positive correlation existed between the PD-1 protein expression frequencies on CD4＋ T cells and CD8＋ T cells and the HCV RNA load detected at baseline （r= 0.82 and 0.75 respectively; all P 〈 0.01）. Conclusion The ability of Peg-IFN-α-2a-based antiviral therapy to suppress HCV replication may involve reduction of PD-I protein expres

关 键 词：肝炎  丙型  慢性 干扰素Α-2A T淋巴细胞亚群 

分 类 号：R512.63[医药卫生—内科学]