Influenza is a category C pathogen that has the potential to cause massive loss of human life. Genetically instability of the virus and large animal reservoirs ensure that new strains will continue to cause human pandemics until efficient vaccination strategies can be developed.Antibodies and T cells are important mechanisms of viral clearance and therefore potential targets for vaccination. Although virus-specific memory CDST cells can be primed outside the lungs without very much difficulty, the cells have very little protective value unless they are able to enter the mucosal tissues. The formaldehyde inactivated viruses that are commonly used for vaccination stimulate antibody responses which protective for specific strains of virus, but do not provide cross-protection against other strains. Since influenza viruses change their coat proteins frequently, there is considerable interest in generating more universal vaccines that include T cell epitopes from conserved internal viral proteins. In an optimal situation, the vaccine would boost both antibody and T cell responses simultaneously. In a previously published study we found evidence that although virus-specific antibodies in the respiratory tract did not prevent virus-specific memory CD8 T cells from getting reactivatedin the draining lymph nodes, and becoming secondary effector T cells that later accumulated in the spleen, they did induce a suppressive environment in the lungs which prevented the reactivated memory CDS T cells from accumulating at the site of reinfection. Based on these data we hypothesize that antibody-mediated suppression of the CDST cell response in the lungs is an important mechanism of immune regulation which limits T cell-mediated pathology during pulmonary influenza infection. The experiments to test this hypothesis will be divided into three parts: Aim 1. To determine why proliferating CDST cells do not accumulate in the lung airways of immune mice. Aim 2. To identify the APCs that participate in memory CDST cell reactivation in vivo. Aim 3. To determine the requirements for T cell immunity during live influenza vaccination. RELEVANCE (See instructions):
NIH ExPorter
NIH ExPorter