REGULATORY ROLE OF VIRUS SPECIFIC CD8ANDT LYMPHOCYTES

尽管哮喘的几个危险因素已经被定义，但其病因 对于儿童哮喘，人们仍然知之甚少。具体地说， 病毒性呼吸道感染在本病发生发展中的作用 仍然存在争议。感染呼吸道病毒，如 呼吸道合胞病毒(RSV)，据报道易患 儿童随后会发展成哮喘。相比之下，一些人 流行病学研究表明，人类的病毒感染 呼吸道可能有保护作用，防止发展为 这种病。 在大多数哮喘患者，特别是儿童中，使人过敏和 暴露于过敏原是哮喘发病的主要危险因素。 近年来，CD4T细胞在慢性粒细胞白血病的发生发展中起着至关重要的作用。 过敏反应已经变得很明显。特别是CD4T细胞，它们是 能够产生IL-4和IL-5(Th2 T细胞)是 建立过敏反应。来自人类和动物的最新证据 研究也证明了CD4T细胞亚群的重要性 病毒感染中的细胞。在RSV感染的小鼠模型中， 对RSV-G(附着)糖蛋白的致敏作用导致强烈的 Th2反应和易感性使动物发生过敏反应 肺部发炎。洞察影响经济增长的因素 CD4T细胞亚群的分化和激活是 因此对了解病毒的作用极其重要 哮喘发展过程中的感染。 最近，一项研究表明，Th2的强烈诱导 RSV-G糖蛋白的应答与CD8T缺乏记忆有关 针对这种抗原的细胞反应。这表明，病毒特异性 CD8T细胞可能在Th2应答的调节中发挥重要作用。 本提案中概述的研究旨在检查 病毒特异性CD8T细胞对Th2CD4T细胞分化的影响 表型。具体地说，研究将集中在1)CD8 T细胞的作用 在调节CD4T细胞分化中的作用及其影响 CD4T细胞分化动力学的调控，2)分子 CD8 T细胞在这一调节中的作用机制，以及3)其影响 对呼吸道合胞病毒动物模型中过敏性炎症的调节作用 感染。将进行研究，以检查呼吸系统的作用 病毒感染对人类变应原特异性T细胞反应的影响。论文 研究将导致对病毒特异性CD8 T作用的新见解 细胞在过敏性肺部疾病发展中的作用。

Although several risk factors for asthma have been defined the etiology for childhood asthma remains poorly understood. In particular, the role of viral respiratory tract infection in the development of this disease remains controversial. Infection with respiratory viruses, such as Respiratory Syncytial Virus (RSV), has been reported to predispose children to the subsequent development of asthma. In contrast, some epidemiologic studies have suggested that viral infection of the respiratory tract may have a protective effect against the development of this disease. In a major of asthmatic patients, particularly children, sensitizing and exposure to allergens is a major risk factor in the development of asthma. Recently, a critical a critical role of CD4+ T cells in the development of allergic responses has become clear. In particular, CD4+ T cells which are capable of producing IL-4 and IL-5 (Th2 T cells) are required for establishing an allergic response. Recent evidence from human and animal studies have also demonstrated the importance of this subset of CD4+ T cells in viral infections. In a murine model of RSV infection, sensitization to the RSV-G (attachment) glycoprotein results in a strong Th2 response and predisposes the animals to the development of allergic lung inflammation. Insights into the factors regulating the differentiation and activation of this subset of subset of CD4+ T cells is therefore extremely important to the understanding of the role of viral infections in the development of asthma. Recently, a study has demonstrated that the strong induction of a Th2 response by RSV-G glycoprotein is linked to the lack of memory of CD8+ T cell response specific to this antigen. This suggests that virus-specific CD8+ T cell may play an important role in the regulation of Th2 responses. The studies outlined in this proposal are designed to examine the role of virus-specific CD8+ T cells on the differentiation of CD4+ T cells of Th2 phenotype. Specifically, studies will focus on 1) the role of CD8+ T cells in regulating CD4+ T cell differentiation and the impact of this regulation on the kinetic of CD4+ T cell differentiation, 2) the molecular mechanisms employed by CD8+ T cells in this regulation, and 3) the impact of this regulation on allergic inflammation in an animal model of RSV infection. Studies will be carried out to examine the role of respiratory viral infection on allergen-specific T cell responses in human. Theses studies will lead to new insights into the role of virus-specific CD8+ T cells in the development of allergic lung diseases.