This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The immune system is severely compromised in aged individuals. This is characterized by decreased antibody titers, failure to produce germinal centers and high affinity antibodies and decreased CD4+ and CD8+ T cell function. Such decline in immune function is frequently associated with illness arising from influenza infections, hospitalization and mortality in aged individuals. However, the mechanism(s) of this immune dysfunction is largely unknown. Here we postulate that a critical factor in this immune dysfunction lies at the antigen presentation level. More specifically, we hypothesize that dendritic cells (DCs), which are the most efficient antigen-presenting cells in the body are impaired. In this context, the Specific Aims of the current proposal are: 1) To determine the numbers, phenotype, function and microenvironmental localization of DC subsets in aged versus young mice: 2) To determine whether Flt3-Ligand and GM-CSF, cytokines which enhance DC numbers in vivo, stimulate enhanced antigen-specific B and T-cell responses in aged mice; 3) To determine whether Flt3-ligand and GM-CSF confer enhanced protection against influenza in aged mice. This research will provide us with a deeper understanding of DCs in the control immune responses against influenza in the elderly. it should ultimately permit more effective use of DCs and their growth factors for vaccination of the elderly against influenza and other infections.
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