Dendritic cells infected by recombinant modified vaccinia virus Ankara retain immunogenicity in vivo despite in vitro dysfunction.
The administration of recombinant vaccinia virus Ankara (MVA) encoding a CTL epitope (pb9) from a malaria antigen induced activation and maturation of splenic dendritic cells (DCs) in vivo. In contrast, incubation of immature dendritic cells (iDCs) with the MVA, in vitro, resulted in down-regulation of MHC class I molecules and reduced their T-cell stimulatory ability. However, the ability of the infected DC to induce an antigen-specific CTL response, in vivo, remained intact. Furthermore, the administration of recombinant MVA-infected DC, but not pb9 peptide-pulsed DC, boosted and expanded the anti-pb9 CTL response that was primed by pb9 peptide-pulsed DC. These data indicate that despite the ability of poxviruses to impair DC maturation in vivo, the important ability of MVA to boost CD8 T-cell response in vivo is mediated at the level of the infected dendritic cells.
Behboudi
Shahriar
S
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DU, UK. s.bedhoudi@ucl.ac.uk
Moore
Anne
A
Gilbert
Sarah C
SC
Nicoll
Claire L
CL
Hill
Adrian V S
AV
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013268:Stimulation, Chemical; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
D014613:Vaccines, Attenuated; D007371:Interferon-gamma