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Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304
Two classes of nucleic acids, bacterial DNA containing unmethylated
CpG motifs and dsRNA in viruses, induce the production of type I IFN
that contributes to the immunostimulatory effects of these microbial
molecules. Thus, it is important to determine which cells produce type
I IFN in response to CpG DNA and dsRNA.
CD4+CD11c- type 2 dendritic cell precursors
(pre-DC2) were identified as the main producers of type I IFN in human
blood in response to viruses. Here we asked whether pre-DC2 also
produce type I IFN in response to CpG DNA and dsRNA.
Oligodeoxynucleotides containing particular palindromic CpG motifs
induced pre-DC2, but not CD11c+ blood DC or monocytes, to
produce IFN-
. In contrast, a synthetic dsRNA, polyinosinic
polycytidylic-acid, induced CD11c+ DC, but not pre-DC2 or
monocytes, to produce IFN-
. These data indicate that CpG DNA and
polyinosinic-polycytidylic acid stimulate different types of cells to
produce type I IFN and that it is important to select
oligodeoxynucleotides containing particular CpG motifs to induce
pre-DC2 to produce type I IFN, which may play a key role in the strong
adjuvant effects of CpG DNA.
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M. Kerkmann, S. Rothenfusser, V. Hornung, A. Towarowski, M. Wagner, A. Sarris, T. Giese, S. Endres, and G. Hartmann Activation with CpG-A and CpG-B Oligonucleotides Reveals Two Distinct Regulatory Pathways of Type I IFN Synthesis in Human Plasmacytoid Dendritic Cells J. Immunol., May 1, 2003; 170(9): 4465 - 4474. [Abstract] [Full Text] [PDF]
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I. Teige, A. Treschow, A. Teige, R. Mattsson, V. Navikas, T. Leanderson, R. Holmdahl, and S. Issazadeh-Navikas IFN-{beta} Gene Deletion Leads to Augmented and Chronic Demyelinating Experimental Autoimmune Encephalomyelitis J. Immunol., May 1, 2003; 170(9): 4776 - 4784. [Abstract] [Full Text] [PDF]
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A. Yonezawa, R. Morita, A. Takaori-Kondo, N. Kadowaki, T. Kitawaki, T. Hori, and T. Uchiyama Natural Alpha Interferon-Producing Cells Respond to Human Immunodeficiency Virus Type 1 with Alpha Interferon Production and Maturation into Dendritic Cells J. Virol., March 15, 2003; 77(6): 3777 - 3784. [Abstract] [Full Text] [PDF]
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H. Tsujimura, T. Tamura, and K. Ozato* Cutting Edge: IFN Consensus Sequence Binding Protein/IFN Regulatory Factor 8 Drives the Development of Type I IFN-Producing Plasmacytoid Dendritic Cells J. Immunol., February 1, 2003; 170(3): 1131 - 1135. [Abstract] [Full Text] [PDF]
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M. Jinushi, T. Takehara, T. Kanto, T. Tatsumi, V. Groh, T. Spies, T. Miyagi, T. Suzuki, Y. Sasaki, and N. Hayashi Critical Role of MHC Class I-Related Chain A and B Expression on IFN-{alpha}-Stimulated Dendritic Cells in NK Cell Activation: Impairment in Chronic Hepatitis C Virus Infection J. Immunol., February 1, 2003; 170(3): 1249 - 1256. [Abstract] [Full Text] [PDF]
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Y. Osugi, S. Vuckovic, and D. N. J. Hart Myeloid blood CD11c+ dendritic cells and monocyte-derived dendritic cells differ in their ability to stimulate T lymphocytes Blood, September 26, 2002; 100(8): 2858 - 2866. [Abstract] [Full Text] [PDF]
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T. Ito, R. Amakawa, T. Kaisho, H. Hemmi, K. Tajima, K. Uehira, Y. Ozaki, H. Tomizawa, S. Akira, and S. Fukuhara Interferon-{alpha} and Interleukin-12 Are Induced Differentially by Toll-like Receptor 7 Ligands in Human Blood Dendritic Cell Subsets J. Exp. Med., June 3, 2002; 195(11): 1507 - 1512. [Abstract] [Full Text] [PDF]
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H. J. Cho, T. Hayashi, S. K. Datta, K. Takabayashi, J. H. Van Uden, A. Horner, M. Corr, and E. Raz IFN-{alpha}{beta} Promote Priming of Antigen-Specific CD8+ and CD4+ T Lymphocytes by Immunostimulatory DNA-Based Vaccines J. Immunol., May 15, 2002; 168(10): 4907 - 4913. [Abstract] [Full Text] [PDF]
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P. Riedl, D. Stober, C. Oehninger, K. Melber, J. Reimann, and R. Schirmbeck Priming Th1 Immunity to Viral Core Particles Is Facilitated by Trace Amounts of RNA Bound to Its Arginine-Rich Domain J. Immunol., May 15, 2002; 168(10): 4951 - 4959. [Abstract] [Full Text] [PDF]
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P. BRANDTZAEG Current Understanding of Gastrointestinal Immunoregulation and Its Relation to Food Allergy Ann. N.Y. Acad. Sci., May 1, 2002; 964(1): 13 - 45. [Abstract] [Full Text] [PDF]
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V. Hornung, S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdorfer, T. Giese, S. Endres, and G. Hartmann Quantitative Expression of Toll-Like Receptor 1-10 mRNA in Cellular Subsets of Human Peripheral Blood Mononuclear Cells and Sensitivity to CpG Oligodeoxynucleotides J. Immunol., May 1, 2002; 168(9): 4531 - 4537. [Abstract] [Full Text] [PDF]
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W. Barchet, M. Cella, B. Odermatt, C. Asselin-Paturel, M. Colonna, and U. Kalinke Virus-induced Interferon {alpha} Production by a Dendritic Cell Subset in the Absence of Feedback Signaling In Vivo J. Exp. Med., February 19, 2002; 195(4): 507 - 516. [Abstract] [Full Text] [PDF]
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D. Verthelyi, R. T. Kenney, R. A. Seder, A. A. Gam, B. Friedag, and D. M. Klinman CpG Oligodeoxynucleotides as Vaccine Adjuvants in Primates J. Immunol., February 15, 2002; 168(4): 1659 - 1663. [Abstract] [Full Text] [PDF]
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C. Buelens, E. J. Bartholome, Z. Amraoui, M. Boutriaux, I. Salmon, K. Thielemans, F. Willems, and M. Goldman Interleukin-3 and interferon beta cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties Blood, February 1, 2002; 99(3): 993 - 998. [Abstract] [Full Text] [PDF]
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P.-O. Vidalain, O. Azocar, H. Yagita, C. Rabourdin-Combe, and C. Servet-Delprat Cytotoxic Activity of Human Dendritic Cells Is Differentially Regulated by Double-Stranded RNA and CD40 Ligand J. Immunol., October 1, 2001; 167(7): 3765 - 3772. [Abstract] [Full Text] [PDF]
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 L. Farkas, K. Beiske, F. Lund-Johansen, P. Brandtzaeg, and F. L. Jahnsen Plasmacytoid Dendritic Cells (Natural Interferon- {{alpha}}/{beta}-Producing Cells) Accumulate in Cutaneous Lupus Erythematosus Lesions Am. J. Pathol., July 1, 2001; 159(1): 237 - 243. [Abstract] [Full Text] [PDF]
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