4.7 Article

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

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JOURNAL OF EXPERIMENTAL MEDICINE
卷 195, 期 10, 页码 1233-1245

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ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20011930

关键词

virus-like particles; dendritic cells; cross-priming; CTL; exogenous antigens

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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.

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