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: 8556100
• 负责人: Barney Graham
• 金额: $ 68.67万
• 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/8556100
• 关键词: Adult; Avidity; CD4 Positive T Lymphocytes; CD8B1 gene; Characteristics; Child; Cytopathology; Cytotoxic T-Lymphocytes; Dendritic Cells; Development; Disease; Epitopes; IL2RA gene; Immune response; Immunization; Infant; Infection; Lower Respiratory Tract Infection; Lung; Mediating; Mus; Neonatal; Property; Regulatory T-Lymphocyte; Respiratory Syncytial Virus Infections; Respiratory syncytial virus; Satellite Viruses; T cell response; T-Lymphocyte; Transgenic Mice; Viral; Virus; Work; cell type; defined contribution; immunopathology; neonate; 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 are currently evaluating lung dendritic cell responses, and the elicitation of adaptive responses in both neonates and adults. This work has been greatly aided within the last year by the development 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 to result in either a beneficial or a detrimental effect.

呼吸道合胞病毒（RSV）是婴幼儿下呼吸道感染的主要原因。RSV感染小鼠的特征在于由CD8+细胞毒性T淋巴细胞（CTL）介导的显著免疫病理学。过去的研究表明，具有不同功能特性和特征的CD8+ T细胞可以在感染或免疫后被诱导，并且可能对病毒清除和RSV相关疾病具有不同的作用。 我们已经描述了新生儿和成人之间的差异引起的RSV感染的CD8+ T细胞反应。 CD8+ T细胞应答的克隆型、功能性亲合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。 我们目前正在评估肺树突状细胞的反应，并在新生儿和成人的适应性反应的启发。 在过去的一年里，通过开发三种具有RSV特异性CD8+ T细胞的转基因小鼠品系，这项工作得到了极大的帮助。 这项研究的继续工作将充分表征CD8+ T细胞对RSV的反应，阐明决定产生的CD8+ T细胞反应类型的重要因素，并帮助了解其他细胞类型如何调节CD8+ T细胞反应，从而产生有益或有害的影响。