Polyomavirus-infected dendritic cells induce antiviral CD8⁺ T lymphocytes

CD8⁺ T cells are critical for the clearance of acute polyomavirus infection and the prevention of polyomavirus-induced tumors, but the antigen- presenting cell(s) involved in generating polyomavirus-specific CD8⁺ T cells have not been defined. We investigated whether dendritic cells and macrophages are permissive for polyomavirus infection and examined their potential for inducing antiviral CD8⁺ T cells. Although dendritic cells and macrophages both supported productive polyomavirus infection, dendritic cells were markedly more efficient at presenting the immunodominant viral epitope to CD8⁺ T cells. Additionally, infected dendritic cells, but not infected macrophages, primed anti-polyomavirus CD8⁺ T cells in vivo. Treatment with Flt3 ligand, a hematopoietic growth factor that dramatically expands the number of dendritic cells, markedly enhanced the magnitude of virus-specific CD8⁺ T-cell responses during acute infection and the pool of memory antipolyomavirus CD8⁺ T cells. These findings suggest that virus-infected dendritic cells induce polyomavirus-specific CD8⁺ T cells in vivo and raise the potential for their use as cellular adjuvants to promote CD8⁺ T cell surveillance against polyomavirus-induced tumors.