RESPIRATORY SYNCYTIAL VIRUS AND ATOPIC PULMONARY RESPONSE

CD 4 + T淋巴细胞在调节细胞凋亡的大小中起着重要作用。 和对感染因子的免疫应答的特征， 环境过敏原现在有大量证据表明 表明Th-2亚群的CD 4 + 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，哮喘和特应性的特征 呼吸道疾病呼吸道合胞病毒（RSV） 是一种主要的人类病原体， 小儿呼吸道感染。RSV在病毒中是独一无二的 病原体中的RSV感染幼儿可导致 病理学变化类似于在过敏性肺病中观察到的 伴有喘息、嗜酸性粒细胞反应和IgE抗体产生。我们 已经检查了RSV在小鼠模型中的免疫应答， 肺RSV感染和年幼儿童队列中。我们 迄今为止的结果表明，CD 8 + T淋巴细胞和遗传 因子可能在调节分化中起重要作用 CD 4 + T淋巴细胞沿着Th-1或Th-2分化途径 以应对RSV感染。本提案中概述的研究 设计用于在鼠模型和人模型中检查 a）8+ T淋巴细胞应答的发展之间的关系 RSV蛋白和CD 4+淋巴细胞反应的发展 Th-2亚型。研究将集中在1）。的结构特点 影响CD 4 + T淋巴细胞的特异性RSV蛋白 差异化，2.）呼吸道合胞病毒特异性CD 8 + T淋巴细胞在呼吸道合胞病毒中的作用 调节CD 4 + Th-1和CD 4 + Th-2 T淋巴细胞的发育 答案，3.）MHC连锁基因和非连锁基因对 对RSV的CD 4 + T淋巴细胞应答。该分析将包括 CD 4 + T淋巴细胞的细胞因子应答的表征 针对RSV-G和F糖蛋白以及CD 8 + T淋巴细胞 有喘息史的儿童对RSV的应答 呼吸道合胞病毒感染或有哮喘病史。拟议的研究 应提供关于CD 8 + T淋巴细胞作用的新信息， 遗传因素在过敏性肺病的发展。

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.