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* University of Minnesota Cancer Center and Department of Pediatrics, and Division of Hematology, Oncology, and Bone Marrow Transplantation, Minneapolis, MN 55455;
Coley Pharmaceutical Group, Wellesley, MA 02481; and
Department of Immunology and Center for Cancer Immunology Research, University of Texas, MD Anderson Cancer Center, Houston, TX 77030
Plasmacytoid dendritic cells (PDCs) are key effectors in host innate immunity and orchestrate adaptive immune responses. CpG oligodeoxynucleotides (ODN) have potent immunostimulatory effects on PDCs through TLR9 recognition and signaling. Little is known about the effects of CpG ODN on human PDC-mediated T cell priming. Here we show that type B CpG ODN effectively promotes PDCs to prime allogeneic naive CD4+CD25– T cells to differentiate into CD4+CD25+ regulatory T (Treg) cells. The CD4+CD25+ T cells induced by CpG ODN-activated PDCs express forkhead transcription factor 3 and produce IL-10, TGF-
, IFN-
, and IL-6, but low IL-2 and IL-4. These CD4+CD25+ T cells are hyporesponsive to secondary alloantigen stimulation and strongly inhibit proliferation of autologous or allogeneic naive CD4+ T cells in an Ag-nonspecific manner. CpG ODN-activated PDCs require direct contact with T cells to induce CD4+CD25+ Treg cells. Interestingly, IL-10 and TGF- were undetectable in the supernatants of CpG ODN-stimulated PDC cultures. Both CpG-A and CpG-C ODN-activated PDCs similarly induced the generation of CD4+CD25+ Treg cells with strong immune suppressive function. This study demonstrates that TLR9 stimulation can promote PDC-mediated generation of CD4+CD25+ Treg cells and suggests PDCs may play an important role in the maintenance of immunological tolerance.
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N. Bendriss-Vermare, S. Burg, H. Kanzler, L. Chaperot, T. Duhen, O. de Bouteiller, M. D'agostini, J.-M. Bridon, I. Durand, J. M. Sederstrom, et al. Virus overrides the propensity of human CD40L-activated plasmacytoid dendritic cells to produce Th2 mediators through synergistic induction of IFN-{gamma} and Th1 chemokine production J. Leukoc. Biol., October 1, 2005; 78(4): 954 - 966. [Abstract] [Full Text] [PDF]
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F Obermeier, U G Strauch, N Dunger, N Grunwald, H C Rath, H Herfarth, J Scholmerich, and W Falk In vivo CpG DNA/toll-like receptor 9 interaction induces regulatory properties in CD4+CD62L+ T cells which prevent intestinal inflammation in the SCID transfer model of colitis Gut, October 1, 2005; 54(10): 1428 - 1436. [Abstract] [Full Text] [PDF]
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A. Chorny, E. Gonzalez-Rey, A. Fernandez-Martin, D. Pozo, D. Ganea, and M. Delgado Vasoactive intestinal peptide induces regulatory dendritic cells with therapeutic effects on autoimmune disorders PNAS, September 20, 2005; 102(38): 13562 - 13567. [Abstract] [Full Text] [PDF]
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M. Rossi and J. W. Young Human Dendritic Cells: Potent Antigen-Presenting Cells at the Crossroads of Innate and Adaptive Immunity J. Immunol., August 1, 2005; 175(3): 1373 - 1381. [Abstract] [Full Text] [PDF]
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G. S. Angelov, M. Tomkowiak, A. Marcais, Y. Leverrier, and J. Marvel Flt3 Ligand-Generated Murine Plasmacytoid and Conventional Dendritic Cells Differ in Their Capacity to Prime Naive CD8 T Cells and to Generate Memory Cells In Vivo J. Immunol., July 1, 2005; 175(1): 189 - 195. [Abstract] [Full Text] [PDF]
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S. Wei, I. Kryczek, L. Zou, B. Daniel, P. Cheng, P. Mottram, T. Curiel, A. Lange, and W. Zou Plasmacytoid Dendritic Cells Induce CD8+ Regulatory T Cells In Human Ovarian Carcinoma Cancer Res., June 15, 2005; 65(12): 5020 - 5026. [Abstract] [Full Text] [PDF]
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B. P.-L. Lee, E. Mansfield, S.-C. Hsieh, T. Hernandez-Boussard, W. Chen, C. W. Thomson, M. S. Ford, S. E. Bosinger, S. Der, Z.-x. Zhang, et al. Expression Profiling of Murine Double-Negative Regulatory T Cells Suggest Mechanisms for Prolonged Cardiac Allograft Survival J. Immunol., April 15, 2005; 174(8): 4535 - 4544. [Abstract] [Full Text] [PDF]
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