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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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E. E. S. Nieuwenhuis, M. F. Neurath, N. Corazza, H. Iijima, J. Trgovcich, S. Wirtz, J. Glickman, D. Bailey, M. Yoshida, P. R. Galle, et al. Disruption of T helper 2-immune responses in Epstein-Barr virus-induced gene 3-deficient mice PNAS, December 24, 2002; 99(26): 16951 - 16956. [Abstract] [Full Text] [PDF]
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A. Chackerian, J. Alt, V. Perera, and S. M. Behar Activation of NKT Cells Protects Mice from Tuberculosis Infect. Immun., November 1, 2002; 70(11): 6302 - 6309. [Abstract] [Full Text] [PDF]
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A. Metwali, A. Blum, D. E. Elliott, and J. V. Weinstock Interleukin-4 Receptor {alpha} Chain and STAT6 Signaling Inhibit Gamma Interferon but Not Th2 Cytokine Expression within Schistosome Granulomas Infect. Immun., October 1, 2002; 70(10): 5651 - 5658. [Abstract] [Full Text] [PDF]
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C. Faveeuw, V. Angeli, J. Fontaine, C. Maliszewski, A. Capron, L. Van Kaer, M. Moser, M. Capron, and F. Trottein Antigen Presentation by CD1d Contributes to the Amplification of Th2 Responses to Schistosoma mansoni Glycoconjugates in Mice J. Immunol., July 15, 2002; 169(2): 906 - 912. [Abstract] [Full Text] [PDF]
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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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