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* Tumor Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom;
Department of Chemistry, University of Konstanz, Konstanz, Germany; and
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan Kettering Cancer Center, New York, NY 10021
Modification in the function of dendritic cells (DC), such as that achieved by microbial stimuli or T cell help, plays a critical role in determining the quality and size of adaptive responses to Ag. NKT cells bearing an invariant TCR (iNKT cells) restricted by nonpolymorphic CD1d molecules may constitute a readily available source of help for DC. We therefore examined T cell responses to i.v. injection of soluble Ag in the presence or the absence of iNKT cell stimulation with the CD1d-binding glycolipid 
-galactosylceramide (-GalCer). Considerably enhanced CD4+ and CD8+ T cell responses were observed when -GalCer was administered at the same time as or close to OVA injection. This enhancement was dependent on the involvement of iNKT cells and CD1d molecules and required CD40 signaling. Studies in IFN-
R-/- mice indicated that IFN- was not required for the adjuvant effect of -GalCer. Consistent with this result, enhanced T cell responses were observed using OCH, an analog of -GalCer with a truncated sphingosine chain and a reduced capacity to induce IFN-. Splenic DC from -GalCer-treated animals expressed high levels of costimulatory molecules, suggesting maturation in response to iNKT cell activation. Furthermore, studies with cultured DC indicated that potentiation of T cell responses required presentation of specific peptide and -GalCer by the same DC, implying conditioning of DC by iNKT cells. The iNKT-enhanced T cell responses resisted challenge with OVA-expressing tumors, whereas responses induced in the absence of iNKT stimulation did not. Thus, iNKT cells exert a significant influence on the efficacy of immune responses to soluble Ag by modulating DC function.
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S.-i. Fujii, K. Shimizu, H. Hemmi, M. Fukui, A. J. Bonito, G. Chen, R. W. Franck, M. Tsuji, and R. M. Steinman Glycolipid {alpha}-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice PNAS, July 25, 2006; 103(30): 11252 - 11257. [Abstract] [Full Text] [PDF]
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H. Lin, M. Nieda, J. F. Hutton, V. Rozenkov, and A. J. Nicol Comparative gene expression analysis of NKT cell subpopulations J. Leukoc. Biol., July 1, 2006; 80(1): 164 - 173. [Abstract] [Full Text] [PDF]
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M.-C. Devilder, S. Maillet, I. Bouyge-Moreau, E. Donnadieu, M. Bonneville, and E. Scotet Potentiation of Antigen-Stimulated V{gamma}9V{delta}2 T Cell Cytokine Production by Immature Dendritic Cells (DC) and Reciprocal Effect on DC Maturation J. Immunol., February 1, 2006; 176(3): 1386 - 1393. [Abstract] [Full Text] [PDF]
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K. Liu, J. Idoyaga, A. Charalambous, S.-i. Fujii, A. Bonito, J. Mordoh, R. Wainstok, X.-F. Bai, Y. Liu, and R. M. Steinman Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells J. Exp. Med., December 5, 2005; 202(11): 1507 - 1516. [Abstract] [Full Text] [PDF]
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S. Oki, C. Tomi, T. Yamamura, and S. Miyake Preferential Th2 polarization by OCH is supported by incompetent NKT cell induction of CD40L and following production of inflammatory cytokines by bystander cells in vivo Int. Immunol., December 1, 2005; 17(12): 1619 - 1629. [Abstract] [Full Text] [PDF]
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S. Patterson, I. Kotsianidis, A. Almeida, M. Politou, A. Rahemtulla, B. Matthew, R. R. Schmidt, V. Cerundolo, I. A. G. Roberts, and A. Karadimitris Human Invariant NKT Cells Are Required for Effective In Vitro Alloresponses J. Immunol., October 15, 2005; 175(8): 5087 - 5094. [Abstract] [Full Text] [PDF]
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S.-Y. Ko, H.-J. Ko, W.-S. Chang, S.-H. Park, M.-N. Kweon, and C.-Y. Kang {alpha}-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor J. Immunol., September 1, 2005; 175(5): 3309 - 3317. [Abstract] [Full Text] [PDF]
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C. Munz, R. M. Steinman, and S.-i. Fujii Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity J. Exp. Med., July 18, 2005; 202(2): 203 - 207. [Abstract] [Full Text] [PDF]
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D. H. Chang, K. Osman, J. Connolly, A. Kukreja, J. Krasovsky, M. Pack, A. Hutchinson, M. Geller, N. Liu, R. Annable, et al. Sustained expansion of NKT cells and antigen-specific T cells after injection of {alpha}-galactosyl-ceramide loaded mature dendritic cells in cancer patients J. Exp. Med., May 2, 2005; 201(9): 1503 - 1517. [Abstract] [Full Text] [PDF]
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J. S. Bezbradica, A. K. Stanic, N. Matsuki, H. Bour-Jordan, J. A. Bluestone, J. W. Thomas, D. Unutmaz, L. Van Kaer, and S. Joyce Distinct Roles of Dendritic Cells and B Cells in Va14Ja18 Natural T Cell Activation In Vivo J. Immunol., April 15, 2005; 174(8): 4696 - 4705. [Abstract] [Full Text] [PDF]
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B. Chung, A. Aoukaty, J. Dutz, C. Terhorst, and R. Tan Cutting Edge: Signaling Lymphocytic Activation Molecule-Associated Protein Controls NKT Cell Functions J. Immunol., March 15, 2005; 174(6): 3153 - 3157. [Abstract] [Full Text] [PDF]
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T. Crough, M. Nieda, and A. J. Nicol Granulocyte Colony-Stimulating Factor Modulates {alpha}-Galactosylceramide-Responsive Human V{alpha}24+V{beta}11+ NKT Cells J. Immunol., October 15, 2004; 173(8): 4960 - 4966. [Abstract] [Full Text] [PDF]
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D. W. O'Neill, S. Adams, and N. Bhardwaj Manipulating dendritic cell biology for the active immunotherapy of cancer Blood, October 15, 2004; 104(8): 2235 - 2246. [Abstract] [Full Text] [PDF]
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S.-i. Fujii, K. Liu, C. Smith, A. J. Bonito, and R. M. Steinman The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation J. Exp. Med., June 21, 2004; 199(12): 1607 - 1618. [Abstract] [Full Text] [PDF]
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L.-P. Ho, B. C. Urban, L. Jones, G. S. Ogg, and A. J. McMichael CD4-CD8{alpha}{alpha} Subset of CD1d-Restricted NKT Cells Controls T Cell Expansion J. Immunol., June 15, 2004; 172(12): 7350 - 7358. [Abstract] [Full Text] [PDF]
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M. Koschella, D. Voehringer, and H. Pircher CD40 Ligation In Vivo Induces Bystander Proliferation of Memory Phenotype CD8 T Cells J. Immunol., April 15, 2004; 172(8): 4804 - 4811. [Abstract] [Full Text] [PDF]
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