Influenza infection is confined to the lung epithelium and its control depends, among other factors, upon an effective local T lymphocyte response. Protective immunity is correlated with influenza-specific memory T lymphocytes that persist in the airways for extended periods of time. Thus, T lymphocyte recruitment is central for protection and memory to influenza. Control of lymphocyte migration is a complex process mediated by several mechanisms including selectins, integrins and chemokines, and it is orchestrated by early inflammatory signals. However, the early innate cytokines that mediate the recruitment of T lymphocytes during primary influenza infection to the site of infection are not well characterized. The overall goal of this project is to identify the molecular mechanisms that dictate CD8 T lymphocyte recruitment at the onset of infection with influenza virus. First, we will identify the mechanisms that regulate CD8 T cell recruitment and function during influenza infection. Second, we will build on this information to determine how this process is regulated in the lung and how it impacts protection against influenza infection. To develop more effective influenza treatments and vaccines, it is essential that we have a better understanding of the mechanisms that regulate cell-mediated immunity in the lung during influenza infection.
