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[乙型肝炎患者调节性T细胞及分泌的免疫调节细胞因子白细胞介素-10水平的研究]

[Investigation of Regulatory T Cells and Secreted Immunomodulatory Cytokine IL-10 Levels in Patients with Hepatitis B].

作者信息

Tuyji Tok Yeşim, Şener Aslı Gamze, Aksoy Gökmen Ayşegül, Demirdal Tuna, Kaya Selçuk

机构信息

Istanbul University Faculty of Cerrahpasa Medicine, Department of Medical Microbiology, Istanbul, Turkey.

Izmir Katip Celebi University Atatürk Training and Research Hospital, Clinic of Medical Microbiology, Izmir, Turkey.

出版信息

Mikrobiyol Bul. 2020 Apr;54(2):266-278. doi: 10.5578/mb.69340.

Abstract

Hepatitis B infection is still among the most important public health problems worldwide, even great improvements have been made in the treatment strategies. Hepatitis B virus (HBV) replicates itself by entering the liver cells and simultaneously with the antigen release, many antagonistic immune responses are induced by the regulatory cells including T cell (Treg), T helper 17 (Th17), T helper 1 (Th1) and T helper 2 (Th2) cells. The main function of Treg cells is to develop an appropriate immune response against infection and to suppress the immune response if it is not required. Tregs suppress the effector T cells via secreting immune system supressor cytokines such as Transforming Growth Factor-Beta and interleukin (IL)-10 or contact dependent way. Tregs protect cells from immunopathologic damage of HBV specific T cell immune response and also cause viral persistence, cirrhosis, hepatocellular carsinoma (HCC) and autoimmunity but the mechanisms are not clear, yet. In this study, we aimed to determine whether evaluation of Treg cells and cytokine IL-10 levels together in hepatitis B patients is useful that may indicate the disease survey and response to the treatment. The peripheral blood samples of ninety-one volunteers, including 61 HBV infected patients and 30 healthy controls selected from applicants of Infectious Diseases Outpatient/Clinic Service, were taken. Their CD4+CD25highFOXP3+CD152+CD127lowTreg cell distribution were measured by flow cytometry method, using the recently defined markers. The level of IL-10 cytokine released by immunomodulatory cells was determined by quantitative ELISA method. Treg cell percentages of the patients with acute hepatitis B were below the normal range (2-4%) (median= 1.50%, 0.6-3.5) and the difference was statistically significant (p= 0.005). Treg cell percentages of the patients with chronic hepatitis B were higher than the control group (p< 0.05), and it was found to be related to the parameters used in the diagnosis, staging and follow-up of the disease. IL-10 levels were significantly higher in all hepatitis B clinical stages compared to the healthy controls (median= 11.7, 17.3-44.9) (p< 0.05). Also, in parallel with Treg cells, IL-10 levels were correlated with HBV DNA load and HBsAg levels (r= 0.48, p< 0.02). Treg cells and the related cytokine IL-10 are thought to play an important role in the immunology of HBV infection and therefore, promising to follow up the disease and to develop new therapeutic strategies targeting the Treg cell.

摘要

乙型肝炎感染仍然是全球最重要的公共卫生问题之一,即便治疗策略已取得了巨大进步。乙型肝炎病毒(HBV)通过进入肝细胞进行自我复制,同时随着抗原释放,包括调节性T细胞(Treg)、辅助性T细胞17(Th17)、辅助性T细胞1(Th1)和辅助性T细胞2(Th2)在内的调节性细胞会诱导许多拮抗免疫反应。Treg细胞的主要功能是针对感染产生适当的免疫反应,并在不需要时抑制免疫反应。Tregs通过分泌免疫系统抑制细胞因子如转化生长因子-β和白细胞介素(IL)-10或通过接触依赖性方式抑制效应T细胞。Tregs保护细胞免受HBV特异性T细胞免疫反应的免疫病理损伤,但同时也会导致病毒持续存在、肝硬化、肝细胞癌(HCC)和自身免疫,但其机制尚不清楚。在本研究中,我们旨在确定评估乙型肝炎患者的Treg细胞和细胞因子IL-10水平是否有助于疾病监测和治疗反应评估。采集了91名志愿者的外周血样本,其中包括从传染病门诊/诊所服务申请者中选出的61名HBV感染患者和30名健康对照。使用最近定义的标志物,通过流式细胞术方法测量其CD4+CD25highFOXP3+CD152+CD127lowTreg细胞分布。通过定量ELISA方法测定免疫调节细胞释放的IL-10细胞因子水平。急性乙型肝炎患者的Treg细胞百分比低于正常范围(2-4%)(中位数=1.50%,0.6-3.5),差异具有统计学意义(p=0.005)。慢性乙型肝炎患者的Treg细胞百分比高于对照组(p<0.05),且发现其与疾病诊断、分期和随访中使用的参数相关。与健康对照相比,所有乙型肝炎临床阶段的IL-10水平均显著升高(中位数=11.7,17.3-44.9)(p<0.05)。此外,与Treg细胞一样,IL-10水平与HBV DNA载量和HBsAg水平相关(r=0.48,p<0.02)。Treg细胞和相关细胞因子IL-10被认为在HBV感染的免疫学中起重要作用,因此有望用于疾病随访和开发针对Treg细胞的新治疗策略。

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