The Journal of Experimental Medicine
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Published online 13 May 2002 doi:10.1084/jem.20011930
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© Rockefeller University Press, 0022-1007/2002/5/1233/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 10, May 20, 2002 1233-1245

CD8{alpha}2 CD11b+ Dendritic Cells Present Exogenous Virus-like Particles to CD8+ T Cells and Subsequently Express CD8{alpha} and CD205 Molecules

Gabriel Morón1, Paloma Rueda2, Ignacio Casal2 and Claude Leclerc1

1 Unité de Biologie des Régulations Immunitaires, Institut Pasteur, 75724 Paris, France
2 Immunología y Génetica Aplicada, SA, 28037 Madrid, Spain

Address correspondence to Claude Leclerc, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: 33 1 45 68 86 18; Fax: 33 1 45 68 85 40; E-mail: cleclerc{at}pasteur.fr

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 CD8{alpha}- DCs, whereas 15 hours later they are presented mainly by CD8{alpha}+ DCs. After PPV-VLPs processing, a fraction of CD11b+ DCs undergo phenotypic changes, i.e., the up-regulation of CD8{alpha} and CD205 and the loss of CD4 molecules on their surface. The failure to detect mRNA coding for CD8{alpha} in CD11b+ DCs suggests that CD8{alpha} expression by these cells is not due to de novo synthesis. In recombination-activating gene knockout mice (Rag-/-), CD11b+ DCs did not express CD8{alpha} and PPV-VLPs presentation by CD8{alpha}+ DCs was severely diminished. These results indicate that both CD8{alpha}- and CD8{alpha}+ DCs play an important role in the induction of CTL responses by exogenous antigens, such as VLP.

Key Words: virus-like particles • dendritic cells • cross-priming • CTL • exogenous antigens


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