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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2162-2169. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-04-1091. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1091v1 103/6/2162    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rothenfusser, S. Articles by Hartmann, G. Search for Related Content PubMed PubMed Citation Articles by Rothenfusser, S. Articles by Hartmann, G. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CpG-A and CpG-B oligonucleotides differentially enhance human peptide–specific primary and memory CD8+ T-cell responses in vitro Simon Rothenfusser, Veit Hornung, Maha Ayyoub, Stefanie Britsch, Andreas Towarowski, Anne Krug, Anja Sarris, Norbert Lubenow, Daniel Speiser, Stefan Endres, and Gunther Hartmann From the Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich, Germany; the Division of Clinical Onco-immunology, Ludwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and the Institute of Immunology and Transfusion Medicine, University of Greifswald, Germany. Two distinct types of CpG oligodeoxynucleotide (ODN) have been identified that differ in their capacity to stimulate antigen-presenting cells: CpG-A induces high amounts of interferon- (IFN-) and IFN- in plasmacytoid dendritic cells (PDCs), whereas CpG-B induces PDC maturation and is a potent activator of B cells but stimulates only small amounts of IFN- and IFN-. Here we examined the ability of these CpG ODNs to enhance peptide-specific CD8+ T-cell responses in human peripheral blood mononuclear cells (PBMCs). The frequency of influenza matrix–specific "memory" CD8+ T cells was increased by both types of CpG ODN, whereas the frequency of Melan-A specific "naive" CD8+ T cells increased on stimulation with CpG-B but not with CpG-A. The presence of PDCs in PBMCs was required for this CpG ODN-mediated effect. The expanded cells were cytotoxic and produced IFN- on peptide restimulation. Soluble factors induced by CpG-A but not CpG-B increased the granzyme-B content and cytotoxicity of established CD8+ T-cell clones, each of which was IFN-/- dependent. In conclusion, CpG-B seems to be superior for priming CD8+ T-cell responses, and CpG-A selectively enhances memory CD8+ T-cell responses and induces cytotoxicity. These results demonstrate distinct functional properties of CpG-A and CpG-B with regard to CD8 T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Malaspina, S. Moir, A. C. DiPoto, J. Ho, W. Wang, G. Roby, M. A. O'Shea, and A. S. Fauci CpG Oligonucleotides Enhance Proliferative and Effector Responses of B Cells in HIV-Infected Individuals J. Immunol., July 15, 2008; 181(2): 1199 - 1206. [Abstract] [Full Text] [PDF] B. G. Molenkamp, B. J.R. Sluijter, P. A.M. van Leeuwen, S. J.A.M. Santegoets, S. Meijer, P. G.J.T.B. Wijnands, J. B.A.G. Haanen, A. J.M. van den Eertwegh, R. J. Scheper, and T. D. de Gruijl Local Administration of PF-3512676 CpG-B Instigates Tumor-Specific CD8+ T-Cell Reactivity in Melanoma Patients Clin. Cancer Res., July 15, 2008; 14(14): 4532 - 4542. [Abstract] [Full Text] [PDF] D. Valmori, N. E. Souleimanian, V. Tosello, N. Bhardwaj, S. Adams, D. O'Neill, A. Pavlick, J. B. Escalon, C. M. Cruz, A. Angiulli, et al. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming PNAS, May 22, 2007; 104(21): 8947 - 8952. [Abstract] [Full Text] [PDF] A. Faith, E. Peek, J. McDonald, Z. Urry, D. F. Richards, C. Tan, G. Santis, and C. Hawrylowicz Plasmacytoid Dendritic Cells from Human Lung Cancer Draining Lymph Nodes Induce Tc1 Responses Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 360 - 367. [Abstract] [Full Text] [PDF] M. Pashenkov, G. Goess, C. Wagner, M. Hormann, T. Jandl, A. Moser, C. M. Britten, J. Smolle, S. Koller, C. Mauch, et al. Phase II Trial of a Toll-Like Receptor 9-Activating Oligonucleotide in Patients With Metastatic Melanoma J. Clin. Oncol., December 20, 2006; 24(36): 5716 - 5724. [Abstract] [Full Text] [PDF] C. Casati, C. Camisaschi, F. Rini, F. Arienti, L. Rivoltini, F. Triebel, G. Parmiani, and C. Castelli Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity. Cancer Res., April 15, 2006; 66(8): 4450 - 4460. [Abstract] [Full Text] [PDF] M. Kerkmann, L. T. Costa, C. Richter, S. Rothenfusser, J. Battiany, V. Hornung, J. Johnson, S. Englert, T. Ketterer, W. Heckl, et al. Spontaneous Formation of Nucleic Acid-based Nanoparticles Is Responsible for High Interferon-{alpha} Induction by CpG-A in Plasmacytoid Dendritic Cells J. Biol. Chem., March 4, 2005; 280(9): 8086 - 8093. [Abstract] [Full Text] [PDF] B. Jahrsdorfer, L. Muhlenhoff, S. E. Blackwell, M. Wagner, H. Poeck, E. Hartmann, R. Jox, T. Giese, B. Emmerich, S. Endres, et al. 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