注射吸毒者HCV单一感染和HIV/HCV共感染早期促进T细胞免疫衰老的研究  

THE STUDY ON HCV MONOINFECTION AND HIV/HCV COINFECTION ENHANCING T-CELL IMMUNE SENESCENCE IN INJECTING DRUG USERS DURING EARLY INFECTION

作　　者：鲁春霞[1] 郑澜[1] 张军 刘羿[1] 丁杨[1] 后文其 LU Chunxia ZHENG Lan ZHANG Jun LIU Yi DING Yang HOU Wenqi(College of Physical Education, Hunan Normal University, Changsha, 410081 Hunan Provincial Drug Authority, Changsha, 410001)

机构地区：[1]湖南师范大学体育学院,长沙410081 [2]湖南省戒毒管理局,长沙410001

出　　处：《中国药物依赖性杂志》2017年第3期182-188,194,共8页Chinese Journal of Drug Dependence

基　　金：国家自然科学基金项目(16ZD05)

摘　　要：目的:了解注射静脉吸毒者(IDU)丙型肝炎病毒(HCV)单一感染和人类免疫缺陷病毒(HIV)/HCV共感染的关系,探讨其早期促进T细胞免疫衰老的严重程度。方法:调查有静脉注射吸毒史的人群在HCV单一感染和HIV/HCV合并感染时免疫参数的变化。T细胞亚群中端粒长度使用Flow-FISH测量。分析指标包括IDU患者HCV单感染(n=21)、HIV/HCV合并感染(n=23)或多次暴露但未感染(MEU)(n=8)的T细胞上的分化、凋亡标志物和端粒长度在基线t=1和t=2随访中测得的数据时间中位数间隔16.9年的变化,所有数据使用SPSS(SPSS 20.0)统计软件。结果:t=1和t=2之间的中值时间间隔为16.9年。在所有IDU组中,CD4^+和CD8^+T细胞内的端粒长度随时间显著降低(P≤0.012)。在t=1时HCV单纯感染的IDU CD4^+T细胞端粒长度与健康供体的相比显著减少(P<0.008)。HIV/HCV合并的IDU在t=1时CD4^+和CD8^+T细胞端粒长度也比健康供体减少(P≤0.002)。在CD4^+和CD8^+T细胞中,未成熟细胞与成熟、成熟分化细胞相比具有更长的RTL(P<0.001),成熟和成熟分化的细胞具有相似的RTL,表明它们经历可比较的增殖循环,所有T细胞亚群中观察到端粒长度减少,但主要在未成熟T细胞(CD27^+CD57^+)中发现的(P≤0.015)。程序性死亡因子1(PD-1)的表达水平,是慢性病毒疾病的衰竭的标志物和急性感染后的激活标志物。结论:HCV单一感染和HIV/HCV合并感染会促进T细胞免疫系统衰老且数据表明这发生在感染早期,所以HCV和HIV的早期治疗就对减缓免疫系统衰老尤为重要。Objective： To study the correlation among injecting drug users（ IDU） of HCV monoinfection and HIV/HCV coinfection,and analyze the severity by enhancing T-cell immune senescence during early infection.Methods： To investigate the changes of HCV monoinfection and HIV/HCV coinfection on immune parameters in（ ex-） IDU. Telomere length in T cell subsets was measured using Flow-FISH. We analyzed telomere length,differentiation and exhaustion markers on T cells at baseline t = 1 and at follow-up t = 2（ median interval 16. 9 years） in IDU who were： HCV mono-infected（ n = 21）; HIV/HCV coinfected（ n = 23） or multiple exposed but uninfected（ MEU）（ n = 8）. All data were analyzed using SPSS 20 statistics software.Results： The median time interval between t = 1 and t = 2 was 16. 9 years. Telomere length within CD4~＋and CD8~＋T cells decreased significantly over time in all IDU groups（ P≤0. 012）. CD4~＋T-cell telomere length in HCV mono-infected IDU was significantly reduced compared to healthy donors at t = 1（ P 0. 008）. HIV/HCV coinfected IDU had reduced CD4~＋and CD8~＋T-cell telomere lengths（ P≤0. 002） to healthy donors i at t = 1. In the CD4~＋and CD8~＋T cells,immature cells with longer RTL compared with the mature and mature differentiated cells（ P 0. 001）, cell maturation and differentiation was similar to RTL,suggesting that they had comparable proliferation cycle,Telomere length decrease was observed within all T-cell subsets,but mainly found in immature T cells（ CD27~＋CD57~＋）（ P≤ 0. 015）. The expression level of programmed cell death factor 1（ PD-1） is a marker of chronic viral disease failure and a marker of activation after acute infection.Conclusion： HCV mono-infection and HIV/HCV coinfection enhance T-cell immune-senescence. Our data suggests that this occurred early during infection,which warrants early treatment for both HCV and HIV to reduce immune senescence in later life.

关 键 词：注射吸毒者 免疫衰老 HCV HIV 

分 类 号：R392.9[医药卫生—免疫学]