CD8α- CD11b+ dendritic cells present exogenous virus-like particles to CD8+ T cells and subsequently express CD8α and CD205 molecules

被引:112
作者
Morón, G
Rueda, P
Casal, I
Leclerc, C
机构
[1] Inst Pasteur, Unite Biol Regulat Immunitaires, F-75724 Paris 15, France
[2] Immunol & Genet Aplicada SA, Madrid 28037, Spain
关键词
virus-like particles; dendritic cells; cross-priming; CTL; exogenous antigens;
D O I
10.1084/jem.20011930
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 v, hole spleen DC population. In vivo, a few hours after injection, PPV-VLPs are presented exclusively to CD8(+) T cells by CDSalpha(-) 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.
引用
收藏
页码:1233 / 1245
页数:13
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