人类疱疹病毒6型诱导调节性T细胞分化及其潜伏感染机制的初步研究

发布时间：2018-04-19 11:51

本文选题：人类疱疹病毒6型 + 细胞病变效应　；参考：《南京医科大学》2006年博士论文

【摘要】：人类疱疹病毒6型(Human Herpesvirus，HHV-6)属于疱疹病毒β亚科，分为HHV-6A和6B两个亚型。HHV-6是引起婴幼儿急疹(exanthem subitum，ES)的病原，其感染具有广泛的亲组织和细胞嗜性，CD46是HHV-6的受体。HHV-6原发感染后在机体内以两种方式建立持续感染，在整个生命周期中可反复被激活。它是一种重要的免疫抑制病毒，对免疫系统具有广泛的免疫抑制作用，能改变感染细胞免疫分子的表达、干扰细胞因子网络以及抑制免疫功能。越来越多的研究表明HHV-6感染与临床多种疾病相关。调节性T细胞(regulatory T cell，Treg)是近年来发现的一类功能独特的T细胞亚群，它具有免疫低反应性和免疫调节两大功能。Treg细胞主要包括：天然CD4~+CD25~+T细胞、Tr1(T regulatory type 1 cell)细胞和Th3细胞等。天然CD4~+CD25~+T细胞在胸腺内发育成熟，以细胞间直接接触、细胞因子非依赖的方式发挥免疫抑制功能；Tr1以分泌高水平IL-10，低水平IFN-γ，低水平或不分泌IL-2、IL-4为特征；Th3以分泌高水平TGF-β为特征。后两群细胞以细胞因子依赖方式发挥免疫抑制功能，激活后的抑制功能是非特异性的。 Treg细胞的研究除在自身免疫、移植免疫及肿瘤免疫方面受到关注外，在病毒免疫方面也逐渐受到重视。以往的研究发现某些病毒如HCV、EBV、慢性逆转录病毒及HIV等能诱导CD4~+Treg细胞分化，这群细胞不仅阻止由Th1细胞介导的炎性病理及自身免疫病的发展，同时抑制宿主保护性免疫，，引起病毒潜伏或慢性感染以及免疫抑制状态的形成。本课题提出如下设想：HHV-6感染可诱导分化调节性T细胞，形成和维持免疫抑制状态，有助于HHV-6的免疫逃避，使其建立潜伏或持续慢性感染。我们的研究依据是：①HHV-6感染能抑制机体
[Abstract]:Human Herpesvirus 6 (HHV-6) belongs to the subfamily of herpesvirus 尾, divided into two subtypes: HHV-6A and 6B. HHV-6 is the pathogen of infantile rash exanthem subtype ES6.CD46 is the receptor of HHV-6. HHV-6 has two ways to establish persistent infection in the body, which can be repeatedly activated throughout the whole life cycle.It is an important immunosuppressive virus, which has a wide range of immunosuppressive effects on the immune system. It can change the expression of immune molecules in infected cells, interfere with the cytokine network and inhibit the immune function.More and more studies have shown that HHV-6 infection is associated with many clinical diseases.Regulatory T cell regulatory T cell (T cell) is a class of T cell subsets with unique function. It has two major functions of immune hyporesponsiveness and immunomodulation. Treg cells mainly include: natural CD4 ~ CD25 ~ T cell Tr1T regulatory type 1 cell and Th3 cell.The natural CD4 ~ CD25 ~ T cells matured in the thymus and were in direct contact with each other.Cytokine independent manner plays an immunosuppressive function by secreting high levels of IL-10, low levels of IFN- 纬 and low or non-secreting levels of IL-2IL-4. Th3 is characterized by the secretion of high levels of TGF- 尾.The latter two groups of cells play immunosuppressive function in cytokine dependent manner, and the activated inhibition function is nonspecific.In addition to autoimmunity, transplantation immunity and tumor immunity, the study of Treg cells has been paid more and more attention.Previous studies have found that some viruses, such as HCV EBV, chronic retrovirus and HIV, can induce the differentiation of CD4 ~ Treg cells. These cells not only prevent the development of inflammatory pathology and autoimmune disease mediated by Th1 cells, but also inhibit the host protective immunity.Causes latent or chronic infection of the virus and the formation of immunosuppressive states.In this paper, we propose that the infection of: HHV-6 can induce the differentiation of regulatory T cells, form and maintain the immunosuppressive state, contribute to the immune evasion of HHV-6, and make it establish latent or persistent chronic infection.Our research is based on the fact that the infection of 1: 1 HHV-6 inhibits the body.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392

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