Protection of mice against Friend retrovirus infection by vaccination with antigen-loaded, spleen-derived dendritic cells.
Antigen-loaded dendritic cells (DC) have been shown to induce specific immune responses in vivo. In the current study we used Friend virus (FV) as a model to analyze whether a DC vaccine is capable of inducing protective immunity against retroviral infections. Mice were vaccinated twice with spleen-derived DC loaded with FV antigen. All control mice that received DC without antigen developed progressive leukemia after FV challenge. In contrast, five of the 14 vaccines were protected against infection, three recovered from FV-induced disease, and only six progressed to lethal leukemia. Animals that progressed to disease had high viral loads in blood and spleen similar to the control mice. Virus-specific antibody responses were not induced by DC vaccination. In contrast, protection correlated with a vaccine-induced CD8+ T-cell response directed against an immunodominant epitope of FV. CD8+ T-cells were critical for the protective effect of the DC vaccine, since in vivo depletion of these cells from immunized mice prevented their protection. Our results demonstrate that antigen-loaded DC can induce specific cellular immune responses and prevent retrovirus-induced disease.
Reuter
Thorsten
T
Institut fuer Virologie der Universitaet Wuerzburg, Versbacherstr.7, 97078, Germany.
Heldmann
Martina
M
Schimmer
Simone
S
Schepers
Koen
K
Dittmer
Ulf
U
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005622:Friend murine leukemia virus / Q000276:immunology*; D051379:Mice; D012192:Retroviridae Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D013163:Splenomegaly / Q000209:etiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes