NR AVPE
AU Martinez del Hoyo,G.; Lopez-Bravo,M.; Metharom,P.; Ardavin,C.; Aucouturier,P.
TI Prion protein expression by mouse dendritic cells is restricted to the nonplasmacytoid subsets and correlates with the maturation state
QU Journal of Immunology 2006 Nov 1; 177(9): 6137-42
PT journal article; research support, non-u.s. gov't
AB Expression of the physiological cellular prion protein (PrPc) is remarkably regulated during differentiation and activation of cells of the immune system. Among these, dendritic cells (DCs) display particularly high levels of membrane PrPc, 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 PrPc. Highest levels of both PrPc and MHC class II molecules were displayed by lymph node CD8alpha(int) DCs, which represent fully mature cells having migrated from peripheral tissues. Maturation induced by overnight culture resulted in increased levels of surface PrPc, as did in vivo DC activation by bacterial LPS. Studies on Fms-like tyrosine kinase 3 ligand bone marrow-differentiated B220(-) DCs confirmed that PrPc 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 PrPc, both before and after activation by TLR-9 engagement. PrP knockout mice displayed higher numbers of spleen CD8alpha(+) 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 PrPc expression by DCs in the induction of T cell responses, and to the pathophysiology of prion diseases.
IN Das normale Prionprotein wird in Hausmaus-Lymphknoten besonders stark von reifen dendritischen Zellen exprimiert, die aufgrund einer Aktivierung z.B. durch eine bakterielle Infektion von der Peripherie in den Lymphknoten gewandert und gereift sind.
MH Animals; Antigens, CD45/analysis; Antigens, CD8/analysis; *Cell Differentiation; Dendritic Cells/chemistry/*cytology/*immunology; Histocompatibility Antigens Class II/analysis/*metabolism; Interleukin-12/metabolism; Mice; Mice, Knockout; PrPc Proteins/analysis/genetics/*metabolism; Spleen/cytology/immunology; Toll-Like Receptor 4/agonists; Toll-Like Receptor 9/agonists; fms-Like Tyrosine Kinase 3/metabolism
AD Department of Immunology and Oncology, Centro Nacional de Biotecnologia/Consejo Superior de Investigaciones Cientificas, Universidad Autonoma, Madrid, Spain.
SP englisch
PO USA