title: Polyomavirus-infected dendritic cells induce antiviral CD8(+) T lymphocytes.
abstract: 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 anti-polyomavirus 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.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Drake
authors.forename: J M
authors.initials: JM
authors.lastname: Moser
authors.forename: A
authors.initials: A
authors.lastname: Hadley
authors.forename: J D
authors.initials: JD
authors.lastname: Altman
authors.forename: C
authors.initials: C
authors.lastname: Maliszewski
authors.forename: E
authors.initials: E
authors.lastname: Butz
authors.forename: A E
authors.initials: AE
authors.lastname: Lukacher
mesh_terms: D016475:3T3 Cells; D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000821:virology; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D011120:Polyomavirus / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D008565:Membrane Proteins; C084881:flt3 ligand protein