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.
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DU, UK. s.bedhoudi@ucl.ac.uk
Shahriar
S
Behboudi
Anne
A
Moore
Sarah C
SC
Gilbert
Claire L
CL
Nicoll
Adrian V S
AV
Hill
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