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。小鼠呼吸道合胞病毒感染以CD8+细胞毒性T淋巴细胞(CTL)介导的免疫病理为特征。过去的研究表明，感染或免疫后可以激发出具有不同功能属性和特征的CD8+T细胞，并且可能在病毒清除和RSV相关疾病中具有不同的作用。我们已经描述了在RSV感染过程中，新生儿和成人CD8+T细胞反应的差异。CD8+T细胞反应的克隆类型、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等级。我们目前正在评估肺树突状细胞的反应，以及对新生儿和成人适应性反应的激发。在过去的一年里，这项工作得到了三个品系的转基因小鼠的极大帮助，这些转基因小鼠具有RSV特异性的CD8+T细胞。这项研究的继续工作将全面描述CD8+T细胞对RSV的反应，阐明决定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调节CD8+T细胞反应，从而导致有益或有害的影响。