CD8alpha- CD11b+ dendritic cells present exogenous virus-like particles to CD8+ T cells and subsequently express CD8alpha and CD205 molecules.
Recombinant porcine parvovirus virus-like particles (PPV-VLPs) are particulate exogenous antigens that induce a strong, specific cytotoxic T lymphocyte (CTL) response in the absence of adjuvant. In the present report, we demonstrate in vivo that dendritic cells (DCs) present PPV-VLPs to CD8+ T cells after intracellular processing. PPV-VLPs are captured by DCs with a high efficacy, which results in the delivery of these exogenous antigens to 50% of the whole spleen DC population. In vivo, a few hours after injection, PPV-VLPs are presented exclusively to CD8+ T cells by CD8alpha- DCs, whereas 15 hours later they are presented mainly by CD8alpha+ DCs. After PPV-VLPs processing, a fraction of CD11b+ DCs undergo phenotypic changes, i.e., the up-regulation of CD8alpha and CD205 and the loss of CD4 molecules on their surface. The failure to detect mRNA coding for CD8alpha in CD11b+ DCs suggests that CD8alpha expression by these cells is not due to de novo synthesis. In recombination-activating gene knockout mice (Rag-/-), CD11b+ DCs did not express CD8alpha and PPV-VLPs presentation by CD8alpha+ DCs was severely diminished. These results indicate that both CD8alpha- and CD8alpha+ DCs play an important role in the induction of CTL responses by exogenous antigens, such as VLP.
Morón
Gabriel
G
Unité de Biologie des Régulations Immunitaires, Institut Pasteur, 75724 Paris, France.
Rueda
Paloma
P
Casal
Ignacio
I
Leclerc
Claude
C
D000818:Animals; D015703:Antigens, CD; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D028323:Parvovirus, Porcine / Q000276:immunology; D011956:Receptors, Cell Surface / Q000032:analysis / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D015854:Up-Regulation; D014771:Virion / Q000276:immunology
D015703:Antigens, CD; D015704:CD4 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; C093569:DEC-205 receptor; D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; C499308:Rag2 protein, mouse; D011956:Receptors, Cell Surface; C064655:V(D)J recombination activating protein 2; D010047:Ovalbumin