Abstract

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 the multiple mechanisms employed by CTLs to eliminate cells may have differential effects on viral clearance and RSV-associated illness. This study seeks to define the contributions of the different CTL effector mechanisms and CD25+ T regulatory cells to the clearance of primary RSV infection, as well as their relative impact on the virus-associated immunopathology.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005027-07
Application #
7732749
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2008
Total Cost
$625,552
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Ruckwardt, Tracy J; Bonaparte, Kathryn L; Nason, Martha C et al. (2009) Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities. J Virol 83:3019-28
Liu, Jie; Ruckwardt, Tracy J; Chen, Man et al. (2009) Characterization of respiratory syncytial virus M- and M2-specific CD4 T cells in a murine model. J Virol 83:4934-41
Collins, Peter L; Graham, Barney S (2008) Viral and host factors in human respiratory syncytial virus pathogenesis. J Virol 82:2040-55
Rutigliano, John A; Ruckwardt, Tracy J; Martin, Julie E et al. (2007) Relative dominance of epitope-specific CD8+ T cell responses in an F1 hybrid mouse model of respiratory syncytial virus infection. Virology 362:314-9
Rutigliano, John A; Rock, Michael T; Johnson, Amanda K et al. (2005) Identification of an H-2D(b)-restricted CD8+ cytotoxic T lymphocyte epitope in the matrix protein of respiratory syncytial virus. Virology 337:335-43
Rutigliano, John A; Johnson, Teresa R; Hollinger, Tonya N et al. (2004) Treatment with anti-LFA-1 delays the CD8+ cytotoxic-T-lymphocyte response and viral clearance in mice with primary respiratory syncytial virus infection. J Virol 78:3014-23
Rutigliano, John A; Graham, Barney S (2004) Prolonged production of TNF-alpha exacerbates illness during respiratory syncytial virus infection. J Immunol 173:3408-17
Graham, Barney S; Rutigliano, John A; Johnson, Teresa R (2002) Respiratory syncytial virus immunobiology and pathogenesis. Virology 297:1-7
Aung, S; Graham, B S (2000) IL-4 diminishes perforin-mediated and increases Fas ligand-mediated cytotoxicity In vivo. J Immunol 164:3487-93