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CUTTING EDGE |
*
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München and
Department of Dermatology, Ludwig Maximilians Universität München, München, Germany
Synthetic oligodeoxynucleotides containing CpG dinucleotides (CpG-ODN) mimic the immunostimulatory qualities of bacterial DNA. We asked whether immunostimulation by CpG-ODN predisposes for a commitment toward a Th1 vs a Th2 response in Leishmania major infection, a model for a lethal Th2-driven disease, in BALB/c mice. CpG-ODN induced Th1 effector T cells in vitro and conveyed protective immunity to disease-prone BALB/c mice in vivo. Conversion to a Th1-driven resistant phenotype was associated with IL-12 production and maintained the expression of IL-12R ß2-chains. Most strikingly, CpG-ODN were even curative when given as late as 20 days after lethal L. major infection, indicating that CpG-ODN revert an established Th2 response. These findings imply an important role of bacterial DNA and CpG-ODN in the instruction of adaptive immune responses. They also point to the therapeutic potential of CpG-ODN in redirecting curative Th1 responses in Th2-driven disorders.
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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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 M. Hafner, R. Zawatzky, C. Hirtreiter, W. A. Buurman, B. Echtenacher, T. Hehlgans, and D. N. Mannel Antimetastatic Effect of CpG DNA Mediated by Type I IFN Cancer Res., July 1, 2001; 61(14): 5523 - 5528. [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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 E. Handman Leishmaniasis: Current Status of Vaccine Development Clin. Microbiol. Rev., April 1, 2001; 14(2): 229 - 243. [Abstract] [Full Text] [PDF]
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B. Bohle, L. Orel, D. Kraft, and C. Ebner Oligodeoxynucleotides Containing CpG Motifs Induce Low Levels of TNF-{{alpha}} in Human B Lymphocytes: Possible Adjuvants for Th1 Responses J. Immunol., March 15, 2001; 166(6): 3743 - 3748. [Abstract] [Full Text] [PDF]
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R. A. Gramzinski, D. L. Doolan, M. Sedegah, H. L. Davis, A. M. Krieg, and S. L. Hoffman Interleukin-12- and Gamma Interferon-Dependent Protection against Malaria Conferred by CpG Oligodeoxynucleotide in Mice Infect. Immun., March 1, 2001; 69(3): 1643 - 1649. [Abstract] [Full Text] [PDF]
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H. Ito, J. Kurtz, J. Shaffer, and M. Sykes CD4 T Cell-Mediated Alloresistance to Fully MHC-Mismatched Allogeneic Bone Marrow Engraftment Is Dependent on CD40-CD40 Ligand Interactions, and Lasting T Cell Tolerance Is Induced by Bone Marrow Transplantation with Initial Blockade of this Pathway J. Immunol., March 1, 2001; 166(5): 2970 - 2981. [Abstract] [Full Text] [PDF]
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D. Serebrisky, A. A. Teper, C.-K. Huang, S.-Y. Lee, T.-F. Zhang, B. H. Schofield, M. Kattan, H. A. Sampson, and X.-M. Li CpG Oligodeoxynucleotides Can Reverse Th2-Associated Allergic Airway Responses and Alter the B7.1/B7.2 Expression in a Murine Model of Asthma J. Immunol., November 15, 2000; 165(10): 5906 - 5912. [Abstract] [Full Text] [PDF]
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H. Weighardt, C. Feterowski, M. Veit, M. Rump, H. Wagner, and B. Holzmann Increased Resistance Against Acute Polymicrobial Sepsis in Mice Challenged with Immunostimulatory CpG Oligodeoxynucleotides Is Related to an Enhanced Innate Effector Cell Response J. Immunol., October 15, 2000; 165(8): 4537 - 4543. [Abstract] [Full Text] [PDF]
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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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H. Hochrein, M. O'Keeffe, T. Luft, S. Vandenabeele, R. J. Grumont, E. Maraskovsky, and K. Shortman Interleukin (IL)-4 Is a Major Regulatory Cytokine Governing Bioactive IL-12 Production by Mouse and Human Dendritic Cells J. Exp. Med., September 11, 2000; 192(6): 823 - 834. [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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C. Vignes, E. Chiffoleau, P. Douillard, R. Josien, H. Peche, J.-M. Heslan, C. Usal, J.-P. Soulillou, and M. C. Cuturi Anti-TCR-Specific DNA Vaccination Demonstrates a Role for a CD8+ T Cell Clone in the Induction of Allograft Tolerance by Donor-Specific Blood Transfusion J. Immunol., July 1, 2000; 165(1): 96 - 101. [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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H. Shirota, K. Sano, T. Kikuchi, G. Tamura, and K. Shirato Regulation of Murine Airway Eosinophilia and Th2 Cells by Antigen-Conjugated CpG Oligodeoxynucleotides as a Novel Antigen-Specific Immunomodulator J. Immunol., June 1, 2000; 164(11): 5575 - 5582. [Abstract] [Full Text] [PDF]
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B. L. Freidag, G. B. Melton, F. Collins, D. M. Klinman, A. Cheever, L. Stobie, W. Suen, and R. A. Seder CpG Oligodeoxynucleotides and Interleukin-12 Improve the Efficacy of Mycobacterium bovis BCG Vaccination in Mice Challenged with M. tuberculosis Infect. Immun., May 1, 2000; 68(5): 2948 - 2953. [Abstract] [Full Text] [PDF]
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O. Egeter, R. Mocikat, K. Ghoreschi, A. Dieckmann, and M. Röcken Eradication of Disseminated Lymphomas with CpG-DNA Activated T Helper Type 1 Cells from Nontransgenic Mice Cancer Res., March 1, 2000; 60(6): 1515 - 1520. [Abstract] [Full Text]
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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 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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P. Parronchi, F. Brugnolo, F. Annunziato, C. Manuelli, S. Sampognaro, C. Mavilia, S. Romagnani, and E. Maggi Phosphorothioate Oligodeoxynucleotides Promote the In Vitro Development of Human Allergen-Specific CD4+ T Cells into Th1 Effectors J. Immunol., December 1, 1999; 163(11): 5946 - 5953. [Abstract] [Full Text] [PDF]
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D. M. Klinman, J. Conover, and C. Coban Repeated Administration of Synthetic Oligodeoxynucleotides Expressing CpG Motifs Provides Long-Term Protection against Bacterial Infection Infect. Immun., November 1, 1999; 67(11): 5658 - 5663. [Abstract] [Full Text] [PDF]
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L. B. de Arruda Hinds, L. M. Previato, J. O. Previato, Q. Vos, J. J. Mond, and L. M. T. Pecanha Modulation of B-Lymphocyte and NK Cell Activities by Glycoinositolphospholipid Purified from Trypanosoma cruzi Infect. Immun., November 1, 1999; 67(11): 6177 - 6180. [Abstract] [Full Text] [PDF]
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J. Fensterle, L. Grode, J. Hess, and S. H. E. Kaufmann Effective DNA Vaccination Against Listeriosis by Prime/Boost Inoculation with the Gene Gun J. Immunol., October 15, 1999; 163(8): 4510 - 4518. [Abstract] [Full Text] [PDF]
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S. Iho, T. Yamamoto, T. Takahashi, and S. Yamamoto Oligodeoxynucleotides Containing Palindrome Sequences with Internal 5'-CpG-3' Act Directly on Human NK and Activated T Cells to Induce IFN-{gamma} Production In Vitro J. Immunol., October 1, 1999; 163(7): 3642 - 3652. [Abstract] [Full Text] [PDF]
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M. R. Stämpfli, G. Scott Neigh, R. E. Wiley, M. Cwiartka, S. A. Ritz, M. M. Hitt, Z. Xing, and M. Jordana Regulation of Allergic Mucosal Sensitization by Interleukin-12 Gene Transfer to the Airway Am. J. Respir. Cell Mol. Biol., September 1, 1999; 21(3): 317 - 326. [Abstract] [Full Text]
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J. Wild, M. J. Grusby, R. Schirmbeck, and J. Reimann Priming MHC-I-Restricted Cytotoxic T Lymphocyte Responses to Exogenous Hepatitis B Surface Antigen Is CD4+ T Cell Dependent J. Immunol., August 15, 1999; 163(4): 1880 - 1887. [Abstract] [Full Text] [PDF]
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 G. Hartmann, G. J. Weiner, and A. M. Krieg CpG DNA: A potent signal for growth, activation, and maturation of human dendritic cells PNAS, August 3, 1999; 96(16): 9305 - 9310. [Abstract] [Full Text] [PDF]
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K. J. Stacey and J. M. Blackwell Immunostimulatory DNA as an Adjuvant in Vaccination against Leishmania major Infect. Immun., August 1, 1999; 67(8): 3719 - 3726. [Abstract] [Full Text] [PDF]
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D. Piedrafita, D. Xu, D. Hunter, R. A. Harrison, and F. Y. Liew Protective Immune Responses Induced by Vaccination with an Expression Genomic Library of Leishmania major J. Immunol., August 1, 1999; 163(3): 1467 - 1472. [Abstract] [Full Text] [PDF]
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F. P. Heinzel and R. M. Rerko Cure of Progressive Murine Leishmaniasis: Interleukin 4 Dominance Is Abolished by Transient CD4+ T Cell Depletion and T Helper Cell Type 1-selective Cytokine Therapy J. Exp. Med., June 21, 1999; 189(12): 1895 - 1906. [Abstract] [Full Text] [PDF]
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K. L. Elkins, T. R. Rhinehart-Jones, S. Stibitz, J. S. Conover, and D. M. Klinman Bacterial DNA Containing CpG Motifs Stimulates Lymphocyte-Dependent Protection of Mice Against Lethal Infection with Intracellular Bacteria J. Immunol., February 15, 1999; 162(4): 2291 - 2298. [Abstract] [Full Text] [PDF]
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