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 continuing characterization of three strains of transgenic mice with CD8+ T cells specific for RSV and we have characterized the response to RSV infection of two T cell clones in mice in vivo. We have recently generated CD4+ T cell transgenic mice and aim to characterize these T cell population as well. Importantly, we have demonstrated that intranasal vaccination with MCMV vectors expressing RSV antigens promotes tissue-resident memory CD8+ T cells which protect against RSV challenge. Finally, we have collaborated with a group at Leiden Institute of Chemistry to investigate mechanisms of controlling CD8+ T cell recognition using chemical methods. These types of approaches can be useful for controlling the induction and function of CD8+ T cells. 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.
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