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CUTTING EDGE |
-Galactosylceramide Directs Conventional T Cells to the Acquisition of a Th2 Phenotype




*
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232;
Pharmaceutical Research Laboratory, Kirin Brewery Co, Ltd., Takasaki-shi, Gunma, Japan; and
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
NK T cells recognize glycolipid Ags such as
-galactosylceramide (
-GalCer) presented by the MHC class I-like
molecule CD1d. In this paper we have studied the in vivo effects of
-GalCer on the generation of adaptive immune responses. Treatment of
mice with
-GalCer resulted in rapid activation of NK T cells and
production of the cytokines IL-4 and IFN-
. However, after this
initial stimulation, NK T cells became polarized for the production of
IL-4. Further, as soon as 6 days after
-GalCer injection, a marked
increase in serum IgE levels was observed. Administration of
-GalCer
at the time of priming of mice with protein Ag resulted in the
generation of Ag-specific Th2 cells and a profound increase in the
production of IgE. Collectively, these findings indicate that
-GalCer may be useful for modulating immune responses toward a Th2
phenotype during prophylaxis and therapy.
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L. T. Mars, V. Laloux, K. Goude, S. Desbois, A. Saoudi, L. Van Kaer, H. Lassmann, A. Herbelin, A. Lehuen, and R. S. Liblau Cutting Edge: V{alpha}14-J{alpha}281 NKT Cells Naturally Regulate Experimental Autoimmune Encephalomyelitis in Nonobese Diabetic Mice J. Immunol., June 15, 2002; 168(12): 6007 - 6011. [Abstract] [Full Text] [PDF] |
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T. J. Roberts, V. Sriram, P. M. Spence, M. Gui, K. Hayakawa, I. Bacik, J. R. Bennink, J. W. Yewdell, and R. R. Brutkiewicz Recycling CD1d1 Molecules Present Endogenous Antigens Processed in an Endocytic Compartment to NKT Cells J. Immunol., June 1, 2002; 168(11): 5409 - 5414. [Abstract] [Full Text] [PDF] |
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M. S. Duthie and S. J. Kahn Treatment with {alpha}-Galactosylceramide Before Trypanosoma cruzi Infection Provides Protection or Induces Failure to Thrive J. Immunol., June 1, 2002; 168(11): 5778 - 5785. [Abstract] [Full Text] [PDF] |
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A. L. Marzo, V. Vezys, K. Williams, D. F. Tough, and L. Lefrancois Tissue-Level Regulation of Th1 and Th2 Primary and Memory CD4 T Cells in Response to Listeria Infection J. Immunol., May 1, 2002; 168(9): 4504 - 4510. [Abstract] [Full Text] [PDF] |
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P. Balmer and E. Devaney NK T Cells Are a Source of Early Interleukin-4 following Infection with Third-Stage Larvae of the Filarial Nematode Brugia pahangi Infect. Immun., April 1, 2002; 70(4): 2215 - 2219. [Abstract] [Full Text] [PDF] |
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T. R. Johnson, S. Hong, L. Van Kaer, Y. Koezuka, and B. S. Graham NK T Cells Contribute to Expansion of CD8+ T Cells and Amplification of Antiviral Immune Responses to Respiratory Syncytial Virus J. Virol., March 27, 2002; 76(9): 4294 - 4303. [Abstract] [Full Text] [PDF] |
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G. Gonzalez-Aseguinolaza, L. Van Kaer, C. C. Bergmann, J. M. Wilson, J. Schmieg, M. Kronenberg, T. Nakayama, M. Taniguchi, Y. Koezuka, and M. Tsuji Natural Killer T Cell Ligand {alpha}-Galactosylceramide Enhances Protective Immunity Induced by Malaria Vaccines J. Exp. Med., March 4, 2002; 195(5): 617 - 624. [Abstract] [Full Text] [PDF] |
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J. E. Gumperz, S. Miyake, T. Yamamura, and M. B. Brenner Functionally Distinct Subsets of CD1d-restricted Natural Killer T Cells Revealed by CD1d Tetramer Staining J. Exp. Med., March 4, 2002; 195(5): 625 - 636. [Abstract] [Full Text] [PDF] |
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A. Bendelac and R. Medzhitov Adjuvants of Immunity: Harnessing Innate Immunity to Promote Adaptive Immunity J. Exp. Med., March 4, 2002; 195(5): F19 - F23. [Full Text] [PDF] |
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M. J. Smyth, N. Y. Crowe, D. G. Pellicci, K. Kyparissoudis, J. M. Kelly, K. Takeda, H. Yagita, and D. I. Godfrey Sequential production of interferon-gamma by NK1.1+ T cells and natural killer cells is essential for the antimetastatic effect of alpha -galactosylceramide Blood, February 15, 2002; 99(4): 1259 - 1266. [Abstract] [Full Text] [PDF] |
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A. W. Jahng, I. Maricic, B. Pedersen, N. Burdin, O. Naidenko, M. Kronenberg, Y. Koezuka, and V. Kumar Activation of Natural Killer T Cells Potentiates or Prevents Experimental Autoimmune Encephalomyelitis J. Exp. Med., December 17, 2001; 194(12): 1789 - 1799. [Abstract] [Full Text] [PDF] |
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A. K. Singh, M. T. Wilson, S. Hong, D. Olivares-Villagomez, C. Du, A. K. Stanic, S. Joyce, S. Sriram, Y. Koezuka, and L. Van Kaer Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis J. Exp. Med., December 17, 2001; 194(12): 1801 - 1811. [Abstract] [Full Text] [PDF] |
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Y. Yang, M. Bao, and J.-W. Yoon Intrinsic Defects in the T-Cell Lineage Results in Natural Killer T-Cell Deficiency and the Development of Diabetes in the Nonobese Diabetic Mouse Diabetes, December 1, 2001; 50(12): 2691 - 2699. [Abstract] [Full Text] [PDF] |
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K. Kawakami, Y. Kinjo, K. Uezu, S. Yara, K. Miyagi, Y. Koguchi, T. Nakayama, M. Taniguchi, and A. Saito Monocyte Chemoattractant Protein-1-Dependent Increase of V{alpha}14 NKT Cells in Lungs and Their Roles in Th1 Response and Host Defense in Cryptococcal Infection J. Immunol., December 1, 2001; 167(11): 6525 - 6532. [Abstract] [Full Text] [PDF] |
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K. Kawakami, Y. Kinjo, S. Yara, K. Uezu, Y. Koguchi, M. Tohyama, M. Azuma, K. Takeda, S. Akira, and A. Saito Enhanced Gamma Interferon Production through Activation of Valpha 14+ Natural Killer T Cells by alpha -Galactosylceramide in Interleukin-18-Deficient Mice with Systemic Cryptococcosis Infect. Immun., November 1, 2001; 69(11): 6643 - 6650. [Abstract] [Full Text] [PDF] |
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S. Muhammad Ali Tahir, O. Cheng, A. Shaulov, Y. Koezuka, G. J. Bubley, S. B. Wilson, S. P. Balk, and M. A. Exley Loss of IFN-{gamma} Production by Invariant NK T Cells in Advanced Cancer J. Immunol., October 1, 2001; 167(7): 4046 - 4050. [Abstract] [Full Text] [PDF] |
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B. Wang, Y.-B. Geng, and C.-R. Wang CD1-restricted NK T Cells Protect Nonobese Diabetic Mice from Developing Diabetes J. Exp. Med., August 6, 2001; 194(3): 313 - 320. [Abstract] [Full Text] [PDF] |
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Z. Trobonjaca, F. Leithauser, P. Moller, R. Schirmbeck, and J. Reimann Activating Immunity in the Liver. I. Liver Dendritic Cells (but Not Hepatocytes) Are Potent Activators of IFN-{gamma} Release by Liver NKT Cells J. Immunol., August 1, 2001; 167(3): 1413 - 1422. [Abstract] [Full Text] [PDF] |
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Y. Hayakawa, K. Takeda, H. Yagita, L. Van Kaer, I. Saiki, and K. Okumura Differential Regulation of Th1 and Th2 Functions of NKT Cells by CD28 and CD40 Costimulatory Pathways J. Immunol., May 15, 2001; 166(10): 6012 - 6018. [Abstract] [Full Text] [PDF] |
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M. A. Exley, N. J. Bigley, O. Cheng, S. M. A. Tahir, S. T. Smiley, Q. L. Carter, H. F. Stills, M. J. Grusby, Y. Koezuka, M. Taniguchi, et al. CD1d-reactive T-cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus J. Leukoc. Biol., May 1, 2001; 69(5): 713 - 718. [Abstract] [Full Text] |
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V. Laloux, L. Beaudoin, D. Jeske, C. Carnaud, and A. Lehuen NK T Cell-Induced Protection Against Diabetes in V{{alpha}}14-J{{alpha}}281 Transgenic Nonobese Diabetic Mice Is Associated with a Th2 Shift Circumscribed Regionally to the Islets and Functionally to Islet Autoantigen J. Immunol., March 15, 2001; 166(6): 3749 - 3756. [Abstract] [Full Text] [PDF] |
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Z. Trobonjaca, F. Leithauser, P. Moller, H. Bluethmann, Y. Koezuka, H. R. MacDonald, and J. Reimann MHC-II-Independent CD4+ T Cells Induce Colitis in Immunodeficient RAG-/- Hosts J. Immunol., March 15, 2001; 166(6): 3804 - 3812. [Abstract] [Full Text] [PDF] |
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B. Wang, T. Chun, I. C. Rulifson, M. Exley, S. P. Balk, and C.-R. Wang Human CD1d Functions as a Transplantation Antigen and a Restriction Element in Mice J. Immunol., March 15, 2001; 166(6): 3829 - 3836. [Abstract] [Full Text] [PDF] |
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A. Karadimitris, S. Gadola, M. Altamirano, D. Brown, A. Woolfson, P. Klenerman, J.-L. Chen, Y. Koezuka, I. A. G. Roberts, D. A. Price, et al. From the Cover: Human CD1d-glycolipid tetramers generated by in vitro oxidative refolding chromatography PNAS, March 13, 2001; 98(6): 3294 - 3298. [Abstract] [Full Text] [PDF] |
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M. C. Leite-de-Moraes, A. Hameg, M. Pacilio, Y. Koezuka, M. Taniguchi, L. Van Kaer, E. Schneider, M. Dy, and A. Herbelin IL-18 Enhances IL-4 Production by Ligand-Activated NKT Lymphocytes: A Pro-Th2 Effect of IL-18 Exerted Through NKT Cells J. Immunol., January 15, 2001; 166(2): 945 - 951. [Abstract] [Full Text] [PDF] |
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