慢性HBV感染者不同免疫状态下及抗病毒治疗后外周血T细胞亚群比例和细胞因子水平特点  

Characteristics of T-cell subsets and serum cytokines in patients with chronic hepatitis B during different immune status and after antivirus treatment

作　　者：杨晨辰[1] 黄睿[1] 刘勇[2] 严晓敏[1] 武抗抗 曹淑凤[1] 唐勤[1] 孙静[1] 吴超[1] 

机构地区：[1]南京医科大学鼓楼临床医学院感染科,南京市210008 [2]南京医科大学鼓楼临床医学院科研部,南京市210008

出　　处：《中华实验和临床感染病杂志（电子版）》2014年第2期35-40,共6页Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)

基　　金：江苏省医学领军人才与创新团队资助项目(No.LJ201154);江苏省临床医学科技专项项目(No.BL2012034);南京市医学科技发展重点项目(No.ZKX10015)

摘　　要：目的：观察不同免疫状态的慢性乙型肝炎病毒（HBV）感染者及抗病毒治疗后外周血CD4^＋T、CD8^＋T细胞比例、CD4^＋/CD8^＋比值及血清中细胞因子IL-6、IL-10、TNF-α和IFN-γ水平的变化特点及与HBeAg血清学转换的相关性。方法纳入79例处于不同免疫状态的慢性HBV感染者（其中非活动性HBV携带期15例、免疫耐受期20例、免疫活化期44例）及21例健康对照者为研究对象，采用流式细胞术检测其外周血CD4^＋T、CD8^＋T细胞比例。对其中33例免疫活化期患者进行核苷（酸）类似物抗病毒治疗并随访至48周。分别于治疗前（T0期）及治疗后4周（T1期）、8周（T2期）、12周（T3期）、24周（T4期）和48周（T5期）采集外周血，流式细胞术检测各时间点患者外周血CD4^＋T、CD8^＋T细胞比例。同时对部分患者血清标本中的细胞因子水平进行检测。结果在慢性HBV感染者中，免疫活化组患者外周血CD4^＋T细胞比例及CD4^＋/CD8^＋比值显著低于健康对照组（P均＜0.05），而CD8^＋T细胞比例显著高于健康对照组（F =3.610，P ＜0.05）。抗病毒治疗后，△T0～T1、△T0～T2期，HBeAg血清学转换组外周血CD8^＋T细胞比例升高率显著高于未转换组（P均＜0.05）；△T0～T5期，HBeAg血清学转换组外周血CD4^＋T细胞比例升高率显著高于未转换组（Z =-2.200，P ＜0.05）。免疫活化组患者血清IL-10、IFN-γ水平均显著高于对照组和免疫耐受组（P均＜0.05）。免疫活化组患者抗病毒治疗后12周及24周，血清IL-10水平显著下降（t=3.037、3.180，P均＜0.05），与ALT水平、HBV DNA载量呈正相关关系（P均＜0.05）。结论慢性HBV感染者在不同免疫状态下外周血T细胞亚群比例及血清细胞因子水平表现不同，免疫活化期患者与健康对照者比CD4^＋T比例及CD4^＋/CD8^＋下降，CD8^＋T比例升高，血清IL-10水平显著升高。HBeAg阳性患者，核苷（�Objective To investigate the percentages of CD4^＋T and CD8^＋T cells in the peripheral blood and serum cytokine levels （IL-6, IL-10, IFN-γand TNF-α） in patients with chronic hepatitis B virus （HBV） infection during different immune status and explore the association between the percentages of T cell subsets and HBeAg seroconversion. Methods Seventy-nine patients with chronic HBV infection as well as 21 healthy donors were enrolled in this study. Blood samples were collected for detecting the percentages of CD4^＋T and CD8^＋T cells by lfow cytometry. Thirty-three HBeAg positive CHB patients received antivira nbsp;treatment were successfully followed for 48 weeks. At the end of 48 weeks, 7 of 33 HBeAg positive CHB paitents achieved HBeAg seroconversion. The percentages of CD4^＋T and CD8^＋T cells were detected at ifve time points of antivirus treatment：T1 （4 week）, T2 （8 week）, T3 （12 week）, T4 （24 week） and T5 （48 week）. Serum cytokine levels were also detected by cytometric bead array （CBA）. Results As compared with normal controls, the percentage of CD4^＋T cell and the ratio of CD4^＋/CD8^＋were lower in patients in the immune reactive phase （P all〈0.05）. However, the percentage of CD8^＋T cell was higher than normal controls （F=3.610, P〈0.05）. During the same monitoring period, the HBV DNA loads and ALT levels in patients who achieved HBeAg seroconversion decreased signiifcantly compared with patients without HBeAg seroconversion. Besides, the increase of CD8^＋T cells duing the periodΔT0-T1 andΔT0-T2 and the increase of CD4^＋T cells during periodΔT0-T5 were signiifcantly different between HBeAg seroconversion patients and HBeAg non-seroconversion patients （Z=-2.200, P〈0.05）. The cytokine levels of IL-10 and IFN-γin patients of immune reactive phase were higher than health controls and patients in immune tolerant phase （P all〈0.05）. The cytokine levels of IL-10 decreased signiifcantly at 12 weeks （T3） and 24 weeks （T4） of a

关 键 词：肝炎病毒 乙型 CD4^+T细胞 CD8^+T细胞 细胞因子 核苷(酸)类似物 

分 类 号：R512.62[医药卫生—内科学]