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Amgen Inc., Seattle, WA 98101
The putative counterparts of human plasmacytoid pre-dendritic cells
(pDCs) have been described in vivo in mouse models and very recently in
an in vitro culture system. In this study, we report that large numbers
of bone marrow-derived murine CD11c+B220+ pDCs
can be generated with Flt3 ligand (FL) as the sole exogenous
differentiation/growth factor and that pDC generation is regulated in
vivo by FL because FL-deficient mice showed a major reduction in
splenic pDC numbers. We extensively analyzed bone marrow-derived
CD11c+B220+ pDCs and described their immature
APC phenotype based on MHC class II, activation markers, and chemokine
receptor level of expression. CD11c+B220+ pDCs
showed a nonoverlapping Toll-like receptor pattern of expression
distinct from that of classical CD11c+B220-
dendritic cells and were poor T cell stimulators. Stimulation of
CD11c+B220+ pDCs with oligodeoxynucleotides
containing certain CpG motifs plus CD40 ligand plus GM-CSF led
to increased MHC class II, CD80, CD86, and CD8
expression levels, to
a switch in chemokine receptor expression that affected their
migration, to IFN- and IL-12 secretion, and to the acquisition of
priming capacities for both CD4+ and CD8+
OVA-specific TCR-transgenic naive T cells. Thus, the in vitro
generation of murine pDCs may serve as a useful tool to further
investigate pDC biology as well as the potential role of these cells in
viral immunity and other settings.
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S. Pichyangkul, K. Yongvanitchit, U. Kum-arb, H. Hemmi, S. Akira, A. M. Krieg, D. G. Heppner, V. A. Stewart, H. Hasegawa, S. Looareesuwan, et al. Malaria Blood Stage Parasites Activate Human Plasmacytoid Dendritic Cells and Murine Dendritic Cells through a Toll-Like Receptor 9-Dependent Pathway J. Immunol., April 15, 2004; 172(8): 4926 - 4933. [Abstract] [Full Text] [PDF]
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M. Salio, M. J. Palmowski, A. Atzberger, I. F. Hermans, and V. Cerundolo CpG-matured Murine Plasmacytoid Dendritic Cells Are Capable of In Vivo Priming of Functional CD8 T Cell Responses to Endogenous but Not Exogenous Antigens J. Exp. Med., February 17, 2004; 199(4): 567 - 579. [Abstract] [Full Text] [PDF]
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C. Asselin-Paturel, G. Brizard, J.-J. Pin, F. Briere, and G. Trinchieri Mouse Strain Differences in Plasmacytoid Dendritic Cell Frequency and Function Revealed by a Novel Monoclonal Antibody J. Immunol., December 15, 2003; 171(12): 6466 - 6477. [Abstract] [Full Text] [PDF]
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A. Schneeberger, P. Luhrs, R. Kutil, P. Steinlein, H. Schild, W. Schmidt, and G. Stingl Granulocyte-Macrophage Colony-Stimulating Factor-Based Melanoma Cell Vaccines Immunize Syngeneic and Allogeneic Recipients via Host Dendritic Cells J. Immunol., November 15, 2003; 171(10): 5180 - 5187. [Abstract] [Full Text] [PDF]
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J. Lund, A. Sato, S. Akira, R. Medzhitov, and A. Iwasaki Toll-like Receptor 9-mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells J. Exp. Med., August 4, 2003; 198(3): 513 - 520. [Abstract] [Full Text] [PDF]
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A. D'Amico and L. Wu The Early Progenitors of Mouse Dendritic Cells and Plasmacytoid Predendritic Cells Are within the Bone Marrow Hemopoietic Precursors Expressing Flt3 J. Exp. Med., July 21, 2003; 198(2): 293 - 303. [Abstract] [Full Text] [PDF]
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