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

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RSV感染具有明显的CD8+细胞毒性T淋巴细胞（CTL）介导的免疫病理特征。过去的研究表明，感染或免疫后可诱导具有不同功能特性和特征的CD8+ T细胞，并可能对病毒清除和rsv相关疾病有不同的影响。我们描述了新生儿和成人在RSV感染期间引起的CD8+ T细胞反应的差异。CD8+ T细胞克隆型、功能亲和性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。我们目前正在评估新生儿和成人的肺树突状细胞反应和适应性反应的引发。这项工作在过去一年中得到了三种具有RSV特异性CD8+ T细胞的转基因小鼠株的发展的极大帮助。本研究的后续工作将充分表征CD8+ T对RSV的反应，阐明决定CD8+ T细胞反应类型的重要因素，并有助于理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。

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.