RESPIRATORY SYNCYTIAL VIRUS AND ATOPIC PULMONARY RESPONSE

CD_4~+T淋巴细胞在调节数量上起着中心作用。 以及对感染性病原体的免疫反应的特征和 环境过敏原。现在有大量的证据 提示Th-2亚群中的CD4+T淋巴细胞介导了 IgE抗体反应的发展和病理变化， 例如嗜酸性粒细胞浸润，哮喘和特应性疾病的特征 呼吸道合胞病毒(RSV)疾病 是一种主要的人类病原体，也是由 幼儿的呼吸道感染。RSV在病毒中是独一无二的 引起幼儿呼吸道合胞病毒感染的病原体可导致 与过敏性肺病相似的病理改变 伴有喘息、嗜酸性粒细胞反应和IgE抗体产生。我们 在一种小鼠模型中检测了对RSV的免疫反应 肺部呼吸道合胞病毒感染和一群幼儿。我们的 到目前为止的研究结果表明，CD8+T淋巴细胞和遗传性 因素可能在调节分化中起重要作用 Th-1或Th-2分化途径中CD4+T细胞的表达 以应对呼吸道合胞病毒感染。这项提案中概述的研究 被设计用于在小鼠模型和人类模型中检查 A)8+T淋巴细胞反应与发育的关系 对呼吸道合胞病毒蛋白和CD_4~+淋巴细胞免疫应答的影响 Th-2亚型。研究的重点将是1。)结构特征 影响CD4+T淋巴细胞的RSV特异性蛋白 分化，2.)呼吸道合胞病毒特异性CD8+T淋巴细胞在呼吸道合胞病毒感染中的作用 调节CD_4~+Th-1和CD_4~+Th-2 T淋巴细胞的发育 回复，3。)MHC连锁和非连锁基因对大鼠血管紧张素转换酶的影响 CD4+T淋巴细胞对呼吸道合胞病毒的应答。这项分析将包括 CD_4~+T细胞的细胞因子反应特性 针对RSV-G和F糖蛋白和CD8+T淋巴细胞 有喘息史的儿童对呼吸道合胞病毒的反应 与呼吸道合胞病毒感染或有哮喘史有关。建议进行的研究 应提供有关CD8+T淋巴细胞作用的新信息 遗传因素在过敏性肺部疾病发展中的作用。

CD4+ T lymphocytes play a central role in regulating the magnitude and character of the immune response to infectious agents and environmental allergens. There is now a large body of evidence indicating that CD4+ T lymphocytes of the Th-2 subset mediate the development of the IgE antibody response and the pathologic changes, e.g. eosinophil infiltration, characteristic of asthma and atopic diseases of the respiratory tract Respiratory Syncytial Virus (RSV) is a major human pathogen and the primary cause of morbidity from respiratory infection in young children. RSV is unique among viral pathogens in that RSV infection of young children can result in pathologic changes similar to that observed in allergic lung disease with wheezing, eosinophil responses and IgE antibody production. We have examined the immune response to RSV in a murine model of pulmonary RSV infection and in a cohort of young children. Our results to date suggest that both CD8+ T lymphocyte and genetic factors may play an important role in regulating the differentiation of CD4+ T lymphocytes along the Th-1 or Th-2 differentiation pathway in response to RSV infection. The studies outlined in this proposal are designed to examine in a murine model and in the human the relationship between the development of a)8+ T lymphocyte responses to RSV proteins and the development of CD4+ lymphocyte responses of the Th-2 subtype. Studies will focus on 1.) the structural features of specific RSV proteins which influence CD4+ T lymphocyte differentiation, 2.) the role of RSV specific CD8+ T lymphocyte in regulating the development of CD4+ Th-1 and CD4+ Th-2 T lymphocyte responses, 3.) the affect of MHC linked and unlinked genes on the CD4+ T lymphocyte response to RSV. This analysis will include the characterization of the cytokine response of CD4+ T lymphocytes directed to the RSV-G and F glycoproteins and the CD8+ T lymphocyte response to RSV in children with a history of wheezing in response to RSV infection or with a history of asthma. The proposed studies should provide new information on the role of CD8+ T lymphocyte and genetic factors in the development of allergic pulmonary diseases.