Cytolytic T Cell Activity In Response To Primary RSV Infection In Mice

小鼠原发性 RSV 感染的溶细胞 T 细胞活性

• 批准号: 8745619
• 负责人: Barney Graham
• 金额: $ 64.55万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8745619
• 关键词: Adult; Antiviral Agents; Avidity; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Characteristics; Child; Cytopathology; Cytotoxic T-Lymphocytes; Dendritic Cells; Development; Disease; Epitopes; IL2RA gene; Immune response; Immunization; Infant; Infection; Life; Lower Respiratory Tract Infection; Lung; Mediating; Mus; Neonatal; Population; Property; Regulatory T-Lymphocyte; Respiratory Syncytial Virus Infections; Respiratory syncytial virus; Satellite Viruses; T cell response; T-Lymphocyte; Transgenic Mice; Viral; Virus; Work; age related; cell type; defined contribution; immunopathology; lymph nodes; response

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and small children. RSV infection in mice is characterized by significant immunopathology which is mediated by CD8+ cytotoxic T lymphocytes (CTL). Past studies have suggested that CD8+ T cells with different functional properties and characteristics can be elicited following infection or immunization, and may have differential effects on viral clearance and RSV-associated illness. We have described differences between neonatal and adult CD8+ T cell responses elicited during RSV infection. Differences in clonotype, functional avidity, and other intrinsic parameters of the CD8+ T cell response may help dictate the epitope hierarchy established following infection. We have now defined the dynamics of lung-migratory dendritic cell populations in the lung and lung-draining lymph nodes of RSV-infected mice during early life as compared to adulthood and have determined lung dendritic cell populations that induce RSV-specific adaptive T cell responses following infection. These dendritic cells were found to induce T cell responses in an age-dependent manner, and we have implicated lower costimulatory molecule expression by neonatal dendritic cells as one mechanism for this difference. Our work in the last year has been greatly aided by the development and characterization of three strains of transgenic mice with CD8+ T cells specific for RSV. Continued work on this study will fully characterize CD8+ T responses to RSV, elucidate important factors that dictate the type of CD8+ T cell response that is generated, and help understand how other cell types regulate the CD8+ T cell response in an age-dependent fashion.

呼吸道合胞病毒（RSV）是婴儿和小儿童下呼吸道感染的主要原因。小鼠的RSV感染的特征是显着的免疫病理学，由CD8+细胞毒性T淋巴细胞（CTL）介导。过去的研究表明，在感染或免疫后，可以引起具有不同功能特性和特征的CD8+ T细胞，并且可能对病毒清除率和与RSV相关的疾病具有不同的影响。我们已经描述了在RSV感染期间引起的新生儿和成人CD8+ T细胞反应之间的差异。 CD8+ T细胞响应的克隆型，功能亲和力和其他内在参数的差异可能有助于决定感染后建立的表位层次结构。现在，我们已经定义了与成年相比，在早期生命的RSV感染小鼠的肺和肺排水淋巴结中肺迁移树突状细胞群体的动力学，并确定了感染后诱导RSV特异性适应性T细胞反应的肺树突状细胞群。 发现这些树突状细胞以年龄依赖性的方式诱导T细胞反应，并且我们暗示了新生儿树突状细胞的较低的共刺激分子表达是这种差异的一种机制。 去年我们的工作得到了三种特异性RSV的CD8+ T细胞的转基因小鼠菌株的发展和表征。这项研究的持续研究将充分表征CD8+ T对RSV的反应，并阐明了产生的CD8+ T细胞反应类型的重要因素，并有助于了解其他细胞类型如何以年龄依赖性方式调节CD8+ T细胞反应。