REGULATORY ROLE OF VIRUS SPECIFIC CD8ANDT LYMPHOCYTES

病毒特异性 CD8ANDT 淋巴细胞的调节作用

• 批准号: 2887964
• 负责人: Anon Srikiatkhachorn
• 金额: $ 21.75万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887964
• 关键词: CD8 molecule; SCID mouse; adolescence (12-20); adult human (21+); allergens; clinical research; cytolysins; cytotoxic T lymphocyte; host organism interaction; human subject; interferon gamma; leukocyte activation /transformation; leukopoiesis; microorganism immunology; passive immunization; recombinant virus; respiratory infections; respiratory syncytial virus; rhinitis; rhinovirus; suppressor T lymphocyte; vaccinia virus; virus diseases

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.

虽然哮喘的几个危险因素已被确定， 对儿童哮喘的了解仍然很少。特别是， 病毒性呼吸道感染在本病的发展中 仍然存在争议。呼吸道病毒感染，如 据报道，呼吸道合胞病毒（RSV） 儿童哮喘的后续发展。相比之下，一些 流行病学研究表明， 呼吸道可能对发展有保护作用 这种疾病。 在一个主要的哮喘患者，特别是儿童， 暴露于过敏原是哮喘发展的主要危险因素。 最近，CD 4 + T细胞在恶性肿瘤的发生发展中起着至关重要的作用。 过敏反应已经很明显了。特别是，CD 4 + T细胞， 能够产生IL-4和IL-5（Th 2 T细胞）是 产生过敏反应人类和动物的最新证据 研究也证明了CD 4 + T细胞亚群的重要性， 病毒感染中的细胞。在RSV感染的鼠模型中， 对RSV-G（附着）糖蛋白的致敏作用导致强的 Th 2应答，并使动物易于发生过敏性 肺部炎症深入了解调节 CD 4 + T细胞亚群的该亚群的分化和活化是 因此对于理解病毒的作用非常重要 感染在哮喘发展中的作用。 最近，一项研究表明，Th 2的强诱导 RSV-G糖蛋白的应答与CD 8 + T细胞缺乏记忆有关 对这种抗原有特异性的细胞反应。这表明病毒特异性 CD 8 + T细胞可能在Th 2应答的调节中起重要作用。 本提案中概述的研究旨在审查 病毒特异性CD 8 + T细胞对Th 2型CD 4 + T细胞分化的影响 表型具体而言，研究将集中在1）CD 8 + T细胞的作用 在调节CD 4 + T细胞分化中的作用， 调节CD 4 + T细胞分化的动力学，2）分子 CD 8 + T细胞在这种调节中所采用的机制，以及3） 在RSV动物模型中， 感染将进行研究，以检查呼吸系统的作用， 病毒感染对人类过敏原特异性T细胞应答的影响。论文 研究将导致对病毒特异性CD 8 + T细胞作用的新认识， 细胞在过敏性肺病的发展。