CD8 T cell Immunity to Influenza

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The objective of this project is to acquire new knowledge about the role of the CD8 T cells in protecting against influenza infection. The CD8 T cell response is thought to play a pivotal role in clearing infection and establishing protective immunity from studies in animal models. However, the quantitative and qualitative characteristics of the influenza A virus-specific CD8 T cell response to natural infection and vaccines have not been investigated systematically in the human host. We propose to evaluate influenza A virus-specific CD8 T cells in child populations and adults. Experiments will use multi-color flow cytometry-based techniques which overcome technical obstacles to assessing CD8 T cell immunity in human populations, including children, to characterize CD8 T cells specific for influenza A antigens. Prospective evaluations will be done in all age cohorts who are immunized with inactivated or live attenuated influenza vaccines and in children with natural influenza A infection. The Specific Aims are: 1. To characterize the influenza A-specific CD8 T cell response before and after administration of inactivated influenza vaccine or live attenuated influenza vaccine to children, young adults, and older adults. We hypothesize that immunization will induce effector and memory CD8 T cell responses at different time points, as characterized by specific patterns of multiple phenotypes and T cell functions. We expect responses to differ by vaccine type, and age. 2. To characterize the number, phenotype and functions of influenza A virus-specific effector and memory CD8 T cells in children with acute influenza. To evaluate antiviral CD8 T cell responses in children allows study of the primary CD8 T cell response in naTve exposed, subjects. We hypothesize that CD8 T cell responses induced by natural infection will resemble responses to live vaccine. This project is a component of our coordinated efforts addressing T cell and B cell responses as well as natural killer responses to influenza A using the same cohort of human subjects and will provide new information on the CD8 T cell immunity in the context of the overall host responses to influenza A. This information will be critical for providing enhanced protection during a potential influenza A pandemic while it is naturally occurring or a bioterrorist event.