: Aged individuals suffer from infectious disease with increased frequency and severity. In particular, influenza viruses represent a major cause of illness among elderly individuals. Given that the protective efficacy of vaccination is greatly reduced in the elderly, it is critical that effective vaccination strategies for the elderly be developed for not only protection from natural yearly influenza infection epidemics, but also from potential bioterrorism attacks. An age-related defect in the activation of naive CD4+ T-cells as well a diminished primary CD8+ T-cell response to influenza virus infection has been described, although there is less evidence of a functional defect in the aged CD8+ T-cells. It has been suggested that the defective cellular immune response in the aged is in part due to a loss of diversity in the CD8+ T-cell repertoire. The current research proposal will investigate the CD8+ T-cell deficit in a two pronged approach. First, we will compare the overall and functional diversity of the naive CD8+ repertoire in young aged mice via DNA spectratye analysis. Second, we will examine the diversity in the CD8+ cellular immune response of aged mice as compared to young mice in response to a primary influenza virus vaccination by DNA spectratype analysis. Together, these studies will determine whether an age associated loss of naive T-cell diversity affects immune function in the elderly. These results have relevance in determining the feasibility of some vaccination strategies for the elderly in which defined viral proteins or epitopes may be used as immunogens. Given that a significantly reduced repertoire diversity may result in 'holes' in the T-cell repertoire, these vaccination strategies may prove ineffective in an elderly population requiring alternate approaches. ? ?
