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.
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