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*
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and the
Veterans Affairs Medical Center and Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242
Genetic vaccination depends at least in part on the adjuvant
properties of plasmids, properties that have been ascribed to
unmethylated CpG dinucleotides in bacterial DNA. Because dendritic
cells (DC) participate in the T cell priming that occurs during genetic
vaccination, we reasoned that CpG-containing DNA might activate DC.
Thus, we assessed the effects of CpG oligodeoxynucleotides (CpG ODN) on
Langerhans cell (LC)-like murine fetal skin-derived DC (FSDDC) in vitro
and on LC in vivo. Treatment with CpG ODN as well as LPS induced FSDDC
maturation, manifested by decreased E-cadherin-mediated adhesion,
up-regulation of MHC class II and costimulator molecule expression, and
acquisition of enhanced accessory cell activity. In contrast to LPS,
CpG ODN stimulated FSDDC to produce large amounts of IL-12 but only
small amounts of IL-6 and TNF-
. Injection of CpG ODN into murine
dermis also led to enhanced expression of MHC class II and CD86 Ag by
LC in overlying epidermis and intracytoplasmic IL-12 accumulation in a
subpopulation of activated LC. We conclude that immunostimulatory CpG
ODN stimulate DC in vitro and in vivo. Bacterial DNA-based vaccines may
preferentially elicit Th1-predominant immune responses because they
activate and mobilize DC and induce them to produce large amounts of
IL-12.
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H. Shirota, K. Sano, N. Hirasawa, T. Terui, K. Ohuchi, T. Hattori, and G. Tamura B Cells Capturing Antigen Conjugated with CpG Oligodeoxynucleotides Induce Th1 Cells by Elaborating IL-12 J. Immunol., July 15, 2002; 169(2): 787 - 794. [Abstract] [Full Text] [PDF]
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M. Gierynska, U. Kumaraguru, S.-K. Eo, S. Lee, A. Krieg, and B. T. Rouse Induction of CD8 T-Cell-Specific Systemic and Mucosal Immunity against Herpes Simplex Virus with CpG-Peptide Complexes J. Virol., June 5, 2002; 76(13): 6568 - 6576. [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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Z. K. Ballas, A. M. Krieg, T. Warren, W. Rasmussen, H. L. Davis, M. Waldschmidt, and G. J. Weiner Divergent Therapeutic and Immunologic Effects of Oligodeoxynucleotides with Distinct CpG Motifs J. Immunol., November 1, 2001; 167(9): 4878 - 4886. [Abstract] [Full Text] [PDF]
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Y. Kawarada, R. Ganss, N. Garbi, T. Sacher, B. Arnold, and G. J. Hammerling NK- and CD8+ T Cell-Mediated Eradication of Established Tumors by Peritumoral Injection of CpG-Containing Oligodeoxynucleotides J. Immunol., November 1, 2001; 167(9): 5247 - 5253. [Abstract] [Full Text] [PDF]
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 B. Mui, S. G. Raney, S. C. Semple, and M. J. Hope Immune Stimulation by a CpG-Containing Oligodeoxynucleotide Is Enhanced When Encapsulated and Delivered in Lipid Particles J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1185 - 1192. [Abstract] [Full Text] [PDF]
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T. Luft, M. Rizkalla, T. Y. Tai, Q. Chen, R. I. MacFarlan, I. D. Davis, E. Maraskovsky, and J. Cebon Exogenous Peptides Presented by Transporter Associated with Antigen Processing (TAP)-Deficient and TAP-Competent Cells: Intracellular Loading and Kinetics of Presentation J. Immunol., September 1, 2001; 167(5): 2529 - 2537. [Abstract] [Full Text] [PDF]
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B. R. Blazar, A. M. Krieg, and P. A. Taylor Synthetic unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides are potent stimulators of antileukemia responses in naive and bone marrow transplant recipients Blood, August 15, 2001; 98(4): 1217 - 1225. [Abstract] [Full Text] [PDF]
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C. W. Cutler, R. Jotwani, and B. Pulendran Dendritic Cells: Immune Saviors or Achilles' Heel? Infect. Immun., August 1, 2001; 69(8): 4703 - 4708. [Full Text] [PDF]
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A. Al-Mariri, A. Tibor, P. Mertens, X. De Bolle, P. Michel, J. Godefroid, K. Walravens, and J.-J. Letesson Protection of BALB/c Mice against Brucella abortus 544 Challenge by Vaccination with Bacterioferritin or P39 Recombinant Proteins with CpG Oligodeoxynucleotides as Adjuvant Infect. Immun., August 1, 2001; 69(8): 4816 - 4822. [Abstract] [Full Text] [PDF]
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H. Shirota, K. Sano, N. Hirasawa, T. Terui, K. Ohuchi, T. Hattori, K. Shirato, and G. Tamura Novel Roles of CpG Oligodeoxynucleotides as a Leader for the Sampling and Presentation of CpG-Tagged Antigen by Dendritic Cells J. Immunol., July 1, 2001; 167(1): 66 - 74. [Abstract] [Full Text] [PDF]
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N. Etchart, P.-O. Desmoulins, K. Chemin, C. Maliszewski, B. Dubois, F. Wild, and D. Kaiserlian Dendritic Cells Recruitment and In Vivo Priming of CD8+ CTL Induced by a Single Topical or Transepithelial Immunization Via the Buccal Mucosa with Measles Virus Nucleoprotein J. Immunol., July 1, 2001; 167(1): 384 - 391. [Abstract] [Full Text] [PDF]
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T. De Smedt, E. Butz, J. Smith, R. Maldonado-Lopez, B. Pajak, M. Moser, and C. Maliszewski CD8{alpha}- and CD8{alpha}+ subclasses of dendritic cells undergo phenotypic and functional maturation in vitro and in vivo J. Leukoc. Biol., June 1, 2001; 69(6): 951 - 958. [Abstract] [Full Text] [PDF]
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M. Bauer, V. Redecke, J. W. Ellwart, B. Scherer, J.-P. Kremer, H. Wagner, and G. B. Lipford Bacterial CpG-DNA Triggers Activation and Maturation of Human CD11c-, CD123+ Dendritic Cells J. Immunol., April 15, 2001; 166(8): 5000 - 5007. [Abstract] [Full Text] [PDF]
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S. Jilek, C. Barbey, F. Spertini, and B. Corthesy Antigen-Independent Suppression of the Allergic Immune Response to Bee Venom Phospholipase A2 by DNA Vaccination in CBA/J Mice J. Immunol., March 1, 2001; 166(5): 3612 - 3621. [Abstract] [Full Text] [PDF]
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F.-G. Zhu and J. S. Marshall CpG-containing oligodeoxynucleotides induce TNF-{alpha} and IL-6 production but not degranulation from murine bone marrow-derived mast cells J. Leukoc. Biol., February 1, 2001; 69(2): 253 - 262. [Abstract] [Full Text]
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P. Harle, S. Noisakran, and D. J. J. Carr The Application of a Plasmid DNA Encoding IFN-{{alpha}}1 Postinfection Enhances Cumulative Survival of Herpes Simplex Virus Type 2 Vaginally Infected Mice J. Immunol., February 1, 2001; 166(3): 1803 - 1812. [Abstract] [Full Text] [PDF]
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D. Askew, R. S. Chu, A. M. Krieg, and C. V. Harding CpG DNA Induces Maturation of Dendritic Cells with Distinct Effects on Nascent and Recycling MHC-II Antigen-Processing Mechanisms J. Immunol., December 15, 2000; 165(12): 6889 - 6895. [Abstract] [Full Text] [PDF]
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D. J. Shedlock and D. B. Weiner DNA vaccination: antigen presentation and the induction of immunity J. Leukoc. Biol., December 1, 2000; 68(6): 793 - 806. [Abstract] [Full Text]
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T. L. Warren, S. K. Bhatia, A. M. Acosta, C. E. Dahle, T. L. Ratliff, A. M. Krieg, and G. J. Weiner APC Stimulated by CpG Oligodeoxynucleotide Enhance Activation of MHC Class I-Restricted T Cells J. Immunol., December 1, 2000; 165(11): 6244 - 6251. [Abstract] [Full Text] [PDF]
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C. Brunner, J. Seiderer, A. Schlamp, M. Bidlingmaier, A. Eigler, W. Haimerl, H.-A. Lehr, A. M. Krieg, G. Hartmann, and S. Endres Enhanced Dendritic Cell Maturation by TNF-{alpha} or Cytidine-Phosphate-Guanosine DNA Drives T Cell Activation In Vitro and Therapeutic Anti-Tumor Immune Responses In Vivo J. Immunol., December 1, 2000; 165(11): 6278 - 6286. [Abstract] [Full Text] [PDF]
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F. Meyer, K. T. Wilson, and S. P. James Modulation of Innate Cytokine Responses by Products of Helicobacter pylori Infect. Immun., November 1, 2000; 68(11): 6265 - 6272. [Abstract] [Full Text] [PDF]
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G. J. Weiner The immunobiology and clinical potential of immunostimulatory CpG oligodeoxynucleotides J. Leukoc. Biol., October 1, 2000; 68(4): 455 - 463. [Abstract] [Full Text]
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S. W. Lee, M. K. Song, K. H. Baek, Y. Park, J. K. Kim, C. H. Lee, H.-K. Cheong, C. Cheong, and Y. C. Sung Effects of a Hexameric Deoxyriboguanosine Run Conjugation into CpG Oligodeoxynucleotides on Their Immunostimulatory Potentials J. Immunol., October 1, 2000; 165(7): 3631 - 3639. [Abstract] [Full Text] [PDF]
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J. J. DONNELLY, M. A. LIU, and J. B. ULMER Antigen Presentation and DNA Vaccines Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): S190 - 193. [Abstract] [Full Text] [PDF]
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W. Olszewska, C. D. Partidos, and M. W. Steward Antipeptide Antibody Responses following Intranasal Immunization: Effectiveness of Mucosal Adjuvants Infect. Immun., September 1, 2000; 68(9): 4923 - 4929. [Abstract] [Full Text] [PDF]
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G. B. Lipford, T. Sparwasser, S. Zimmermann, K. Heeg, and H. Wagner CpG-DNA-Mediated Transient Lymphadenopathy Is Associated with a State of Th1 Predisposition to Antigen-Driven Responses J. Immunol., August 1, 2000; 165(3): 1228 - 1235. [Abstract] [Full Text] [PDF]
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A. Kolb-Maurer, I. Gentschev, H.-W. Fries, F. Fiedler, E.-B. Brocker, E. Kampgen, and W. Goebel Listeria monocytogenes-Infected Human Dendritic Cells: Uptake and Host Cell Response Infect. Immun., June 1, 2000; 68(6): 3680 - 3688. [Abstract] [Full Text] [PDF]
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E. Ban, L. Dupre, E. Hermann, W. Rohn, C. Vendeville, B. Quatannens, P. Ricciardi-Castagnoli, A. Capron, and G. Riveau CpG motifs induce Langerhans cell migration in vivo Int. Immunol., June 1, 2000; 12(6): 737 - 745. [Abstract] [Full Text] [PDF]
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 J. S. Waters, A. Webb, D. Cunningham, P. A. Clarke, F. Raynaud, F. di Stefano, and F. E. Cotter Phase I Clinical and Pharmacokinetic Study of Bcl-2 Antisense Oligonucleotide Therapy in Patients With Non-Hodgkin's Lymphoma J. Clin. Oncol., May 9, 2000; 18(9): 1812 - 1823. [Abstract] [Full Text] [PDF]
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R. S. Chu, T. McCool, N. S. Greenspan, J. R. Schreiber, and C. V. Harding CpG Oligodeoxynucleotides Act as Adjuvants for Pneumococcal Polysaccharide-Protein Conjugate Vaccines and Enhance Antipolysaccharide Immunoglobulin G2a (IgG2a) and IgG3 Antibodies Infect. Immun., March 1, 2000; 68(3): 1450 - 1456. [Abstract] [Full Text] [PDF]
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R. M. Vabulas, H. Pircher, G. B. Lipford, H. Hacker, and H. Wagner CpG-DNA Activates In Vivo T Cell Epitope Presenting Dendritic Cells to Trigger Protective Antiviral Cytotoxic T Cell Responses J. Immunol., March 1, 2000; 164(5): 2372 - 2378. [Abstract] [Full Text] [PDF]
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 H. Shirota, K. Sano, T. Kikuchi, G. Tamura, and K. Shirato Regulation of T-helper Type 2 Cell and Airway Eosinophilia by Transmucosal Coadministration of Antigen and Oligodeoxynucleotides Containing CpG Motifs Am. J. Respir. Cell Mol. Biol., February 1, 2000; 22(2): 176 - 182. [Abstract] [Full Text]
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G. Hartmann, R. D. Weeratna, Z. K. Ballas, P. Payette, S. Blackwell, I. Suparto, W. L. Rasmussen, M. Waldschmidt, D. Sajuthi, R. H. Purcell, et al. Delineation of a CpG Phosphorothioate Oligodeoxynucleotide for Activating Primate Immune Responses In Vitro and In Vivo J. Immunol., February 1, 2000; 164(3): 1617 - 1624. [Abstract] [Full Text] [PDF]
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G. Hartmann and A. M. Krieg Mechanism and Function of a Newly Identified CpG DNA Motif in Human Primary B Cells J. Immunol., January 15, 2000; 164(2): 944 - 953. [Abstract] [Full Text] [PDF]
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M. G. Chiaramonte, M. Hesse, A. W. Cheever, and T. A. Wynn CpG Oligonucleotides Can Prophylactically Immunize Against Th2-Mediated Schistosome Egg-Induced Pathology by an IL-12-Independent Mechanism J. Immunol., January 15, 2000; 164(2): 973 - 985. [Abstract] [Full Text] [PDF]
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D. P. Sester, S. J. Beasley, M. J. Sweet, L. F. Fowles, S. L. Cronau, K. J. Stacey, and D. A. Hume Bacterial/CpG DNA Down-Modulates Colony Stimulating Factor-1 Receptor Surface Expression on Murine Bone Marrow-Derived Macrophages with Concomitant Growth Arrest and Factor-Independent Survival J. Immunol., December 15, 1999; 163(12): 6541 - 6550. [Abstract] [Full Text] [PDF]
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