Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and small children. RSV infection 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. This study seeks to fully characterize CD8+ T responses to RSV, elucidate important factors that dictate the type of CD8+ T cell response that is generated, and understand how other cell types regulate the CD8+ T cell response to result in either a beneficial or a detrimental effect.

Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2011
Total Cost
$1,275,378
Indirect Cost
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State
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Ruckwardt, T J; Morabito, K M; Bar-Haim, E et al. (2018) Neonatal mice possess two phenotypically and functionally distinct lung-migratory CD103+ dendritic cell populations following respiratory infection. Mucosal Immunol 11:186-198
Morabito, Kaitlyn M; Ruckwardt, Tracy J; Bar-Haim, Erez et al. (2018) Memory Inflation Drives Tissue-Resident Memory CD8+ T Cell Maintenance in the Lung After Intranasal Vaccination With Murine Cytomegalovirus. Front Immunol 9:1861
Morabito, K M; Ruckwardt, T R; Redwood, A J et al. (2017) Intranasal administration of RSV antigen-expressing MCMV elicits robust tissue-resident effector and effector memory CD8+ T cells in the lung. Mucosal Immunol 10:545-554
Malloy, Allison M W; Ruckwardt, Tracy J; Morabito, Kaitlyn M et al. (2017) Pulmonary Dendritic Cell Subsets Shape the Respiratory Syncytial Virus-Specific CD8+ T Cell Immunodominance Hierarchy in Neonates. J Immunol 198:394-403
Ruckwardt, Tracy J; Morabito, Kaitlyn M; Graham, Barney S (2016) Determinants of early life immune responses to RSV infection. Curr Opin Virol 16:151-157
Morabito, Kaitlyn M; Erez, Noam; Graham, Barney S et al. (2016) Phenotype and Hierarchy of Two Transgenic T Cell Lines Targeting the Respiratory Syncytial Virus KdM282-90 Epitope Is Transfer Dose-Dependent. PLoS One 11:e0146781
Pawlak, Joanna B; Gential, Geoffroy P P; Ruckwardt, Tracy J et al. (2015) Bioorthogonal deprotection on the dendritic cell surface for chemical control of antigen cross-presentation. Angew Chem Int Ed Engl 54:5628-31
Ruckwardt, Tracy J; Malloy, Allison M W; Morabito, Kaitlyn M et al. (2014) Quantitative and qualitative deficits in neonatal lung-migratory dendritic cells impact the generation of the CD8+ T cell response. PLoS Pathog 10:e1003934
Bar-Haim, Erez; Erez, Noam; Malloy, Allison M W et al. (2014) CD8+ TCR transgenic strains expressing public versus private TCR targeting the respiratory syncytial virus K(d)M2(82-90) epitope demonstrate similar functional profiles. PLoS One 9:e99249
Billam, Padma; Bonaparte, Kathryn L; Liu, Jie et al. (2011) T Cell receptor clonotype influences epitope hierarchy in the CD8+ T cell response to respiratory syncytial virus infection. J Biol Chem 286:4829-41

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