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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3713-3722.
Prepublished online as a Blood First Edition Paper on August 12, 2008; DOI 10.1182/blood-2008-03-146290.
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Submitted March 21, 2008
Accepted July 4, 2008
Plasmacytoid dendritic cells efficiently cross-prime naive T cells in vivo after TLR activation
Juliette Mouries, Gabriel Moron, Geraldine Schlecht, Nicolas Escriou, Gilles Dadaglio, and Claude Leclerc*
Regulation Immunitaire et Vaccinologie, Institut Pasteur, Paris, France
Genetique Moleculaire des Virus Respiratoires, Institut Pasteur, Paris, France
INSERM, U 883, Paris, France
* Corresponding author; email: cleclerc{at}pasteur.fr.
Cross-presentation is a crucial mechanism in tumoral and microbial immunity because it allows internalized cell associated or exogenous antigens (Ags) to be delivered into the MHC-I pathway. This pathway is important for the development of CD8+ T-cell responses and for the induction of tolerance. In mice, cross-presentation is considered to be a unique property of CD8 + conventional dendritic cells (DCs). Here, we show that splenic plasmacytoid DCs (pDCs), efficiently capture exogenous Ags in vivo, but are not able to cross-present these Ags at steady state. However, in vitro and in vivo stimulation by Toll like receptor-7, or -9 or viruses licenses pDCs to cross-present soluble or particulate Ags by a TAP-dependent mechanism. Induction of cross-presentation confers to pDCs the ability to generate efficient effector CD8+ T-cell responses against exogenous Ags in vivo showing that pDCs may play a crucial role in induction of adaptive immune responses against pathogens that do not infect tissues of haemopoietic origin. This study provides the first evidence for an in vivo role of splenic pDCs in Ag cross presentation and T-cell cross-priming and suggests that pDCs may constitute an attractive target to boost the efficacy of vaccines based on CTL induction.

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