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Prion Protein Expression by Mouse Dendritic Cells Is Restricted to the Nonplasmacytoid Subsets and Correlates with the Maturation State¹

Gloria Martínez del Hoyo^*, María López-Bravo^*, Patraporn Metharom^2,, Carlos Ardavín^3,4,* and Pierre Aucouturier^3,4,

^* Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, Universidad Autónoma, Madrid, Spain; and Université Pierre et Marie Curie, Unité Mixte de Recherche S Institut National de la Santé et de la Recherche Médicale Unité 712, Paris, France

Expression of the physiological cellular prion protein (PrP^C) is remarkably regulated during differentiation and activation of cells of the immune system. Among these, dendritic cells (DCs) display particularly high levels of membrane PrP^C, which increase upon maturation, in parallel with that of molecules involved in Ag presentation to T cells. Freshly isolated mouse Langerhans cells, dermal DCs, and DCs from thymus, spleen, and mesenteric lymph nodes expressed low to intermediate levels of PrP^C. Highest levels of both PrP^C and MHC class II molecules were displayed by lymph node CD8^int DCs, which represent fully mature cells having migrated from peripheral tissues. Maturation induced by overnight culture resulted in increased levels of surface PrP^C, as did in vivo DC activation by bacterial LPS. Studies on Fms-like tyrosine kinase 3 ligand bone marrow-differentiated B220^– DCs confirmed that PrP^C expression followed that of MHC class II and costimulatory molecules, and correlated with IL-12 production in response to TLR-9 engagement by CpG. However, at variance with conventional DCs, B220⁺ plasmacytoid DCs isolated from the spleen, or in vitro differentiated, did not significantly express PrP^C, both before and after activation by TLR-9 engagement. PrP knockout mice displayed higher numbers of spleen CD8⁺ DCs, but no significant differences in their maturation response to stimulation through TLR-4 and TLR-9 were noticed. Results are discussed in relation to the functional relevance of PrP^C expression by DCs in the induction of T cell responses, and to the pathophysiology of prion diseases.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants from the Ministerio de Educación y Ciencia of Spain SAF-2003-07291, Groupement d’Intéret Scientifique Maladies à Prions, and European Union Contract QLK5-CT-2002-01044. P.M. was a recipient of an Institut National de la Santé et de la Recherche Médicale Poste Vert fellowship.

² Current address: Centre for Research in Vascular Biology, BioSciences Institute, University College, Cork, Ireland.

³ C.A. and P.A. contributed equally to this work.

⁴ Address correspondence and reprint requests to Dr. Pierre Aucouturier, Université Pierre et Marie Curie, Unité Mixte de Recherche S Institut National de la Santé et de la Recherche Médicale Unité 712, 184 rue du Faubourg Saint-Antoine, 75571, Paris Cedex 12, France; E-mail address: aucoutur{at}st-antoine.inserm.fr or Dr. Carlos Ardavín, Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, Universidad Autónoma, 28049 Madrid, Spain; E-mail address: ardavin{at}cnb.uam.es

⁵ Abbreviations used in this paper: PrP, prion protein; DC, dendritic cell; DDC, dermal DC; int, intermediate; LC, Langerhans cell; LN, lymph node; MS-LN, mesenteric LN; pDC, plasmacytoid DC; PrP^C, cellular PrP; Flt3L, Fms-like tyrosine kinase 3 ligand; TC, tricolor; TSE, transmissible spongiform encephalopathy.

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