Abstract

Influenza virus infection is a major cause of increased hospitalization and death among elderly persons when compared to the young. The main objectives of this proposal are to test the hypothesis that the diminished ability of aged mice to clear influenza infection and recover from infection is due to deficient CD8+ cytotoxic T lymphocyte (CTL) activity and to identify the mechanisms responsible for the deficient CD8+ CTL activity.
The specific aims are first, to determine if decreased resistance to influenza virus infection and disease in aged mice is due to diminished CD8+ CTL activity, by immunizing mice with influenza nucleoprotein vaccines. Second, to determine the biologic and molecular basis of deficient CD8+ CTL functions in aged mice by assessing the functional and phenotypic characteristics of CD8+ effector cells and precursor memory CTL in aged mice. Third, to determine if the decline of specific T cell functions with aging correlate with loss of resistance to influenza virus infection, and fourth, to evaluate the capacity for recombinant murine IL-12 and monophosphoryl lipid A adjuvant to reverse the age effects.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG010057-03
Application #
2769312
Study Section
Experimental Virology Study Section (EVR)
Project Start
1996-09-30
Project End
2000-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Mbawuike, Innocent N; Zhang, Yongxin; Couch, Robert B (2007) Control of mucosal virus infection by influenza nucleoprotein-specific CD8+ cytotoxic T lymphocytes. Respir Res 8:44
Zhang, Yongxin; Pacheco, Susan; Acuna, Catherine L et al. (2002) Immunoglobulin A-deficient mice exhibit altered T helper 1-type immune responses but retain mucosal immunity to influenza virus. Immunology 105:286-94
Mbawuike, Innocent N; Zhang, Yongxin; Wang, Ying et al. (2002) Cationic liposome-mediated enhanced generation of human HLA-restricted RSV-specific CD8+ CTL+. J Clin Immunol 22:164-75
Zhang, Y; Wang, Y; Gilmore, X et al. (2002) Apoptosis and reduced influenza A virus specific CD8+ T cells in aging mice. Cell Death Differ 9:651-60
Zhang, Y; Wang, Y; Gilmore, X et al. (2001) Independent and synergistic effects of interleukin-18 and interleukin-12 in augmenting cytotoxic T lymphocyte responses and IFN-gamma production in aging. J Interferon Cytokine Res 21:843-50
Zhang, Y; Acuna, C L; Switzer, K C et al. (2000) Corrective effects of interleukin-12 on age-related deficiencies in IFN-gamma production and IL-12Rbeta2 expression in virus-specific CD8+ T cells. J Interferon Cytokine Res 20:235-45
Mbawuike, I N; Pacheco, S; Acuna, C L et al. (1999) Mucosal immunity to influenza without IgA: an IgA knockout mouse model. J Immunol 162:2530-7
Harriman, G R; Bogue, M; Rogers, P et al. (1999) Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes. J Immunol 162:2521-9
Mbawuike, I N; Acuna, C L; Walz, K C et al. (1997) Cytokines and impaired CD8+ CTL activity among elderly persons and the enhancing effect of IL-12. Mech Ageing Dev 94:25-39
Mbawuike, I N; Acuna, C; Caballero, D et al. (1996) Reversal of age-related deficient influenza virus-specific CTL responses and IFN-gamma production by monophosphoryl lipid A. Cell Immunol 173:64-78