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-Galactosylceramide Specifically Stimulates V14+ NK T Lymphocytes1
*
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121;
Pharmaceutical Research laboratory, Kirin Brewery Co., Takasaki-shi, Gumna, Japan;
Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Department of Medicine, Harvard Medical School, Boston, MA 02115;
§
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111; and
¶
CREST (Core Research for Evolutional Science and Technology) Project, Japan Science and Technology Corporation and Division of Molecular Immunology, Center for Biomedical Science, School of Medicine, Chiba University, Chuo, Chiba, Japan
Mouse CD1 (mCD1) glycoproteins are known to present peptides, while
human CD1 molecules present glycolipids. In mice, mCD1-autoreactive NK
T cells play critical roles in various immune responses, through the
secretion of high amounts of cytokines. This study was initiated to
determine whether glycolipids are involved in the autorecognition of
mCD1 by NK T cells. 
-Galactosylceramide (-GalCer) was the only
glycolipid tested capable of eliciting an mCD1-restricted response by
splenic T cells. Moreover, splenic T cells derived from mCD1-deficient
mice were not stimulated by -GalCer, suggesting that the responsive
T cells are selected by mCD1. Using cytoflow techniques, we confirmed
that, in response to -GalCer, IFN-
-secreting cells displayed an
NK T cell phenotype. The predominance of IFN- vs IL-4, however, is
determined by the type of mCD1+ APC, suggesting the
potential for APC regulation of cytokine production by NK T cells.
Among a panel of 10 mCD1-autoreactive T cell hybridomas, only the ones
that express the typical V14J281 TCR rearrangement of NK T cells
responded to -GalCer. Fixation or treatment of mCD1+
APCs with an inhibitor of endosomal acidification and the use of mCD1
mutants unable to traffic through endosome still allowed -GalCer to
stimulate NK T cells. Thus, endosomal trafficking and Ag processing are
not required for glycolipid recognition. In summary, -GalCer might
be the autologous ligand, or a mimic of a glycolipid ligand, involved
in the mCD1-mediated stimulation of NK T cells.
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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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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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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. D. De Silva, J.-J. Park, N. Matsuki, A. K. Stanic, R. R. Brutkiewicz, M. E. Medof, and S. Joyce Lipid Protein Interactions: The Assembly of CD1d1 with Cellular Phospholipids Occurs in the Endoplasmic Reticulum J. Immunol., January 15, 2002; 168(2): 723 - 733. [Abstract] [Full Text] [PDF]
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M. Mempel, C. Ronet, F. Suarez, M. Gilleron, G. Puzo, L. Van Kaer, A. Lehuen, P. Kourilsky, and G. Gachelin Natural Killer T Cells Restricted by the Monomorphic MHC Class 1b CD1d1 Molecules Behave Like Inflammatory Cells J. Immunol., January 1, 2002; 168(1): 365 - 371. [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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M. Gui, J. Li, L.-J. Wen, R. R. Hardy, and K. Hayakawa TCR{beta} Chain Influences But Does Not Solely Control Autoreactivity of V{alpha}14J281T Cells J. Immunol., December 1, 2001; 167(11): 6239 - 6246. [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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J. A. Hobbs, S. Cho, T. J. Roberts, V. Sriram, J. Zhang, M. Xu, and R. R. Brutkiewicz Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus J. Virol., November 15, 2001; 75(22): 10746 - 10754. [Abstract] [Full Text] [PDF]
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Y. Ikarashi, R. Mikami, A. Bendelac, M. Terme, N. Chaput, M. Terada, T. Tursz, E. Angevin, F. A. Lemonnier, H. Wakasugi, et al. Dendritic Cell Maturation Overrules H-2d-Mediated Natural Killer T (Nkt) Cell Inhibition: Critical Role for B7 in Cd1d-Dependent Nkt Cell Interferon {gamma} Production J. Exp. Med., October 15, 2001; 194(8): 1179 - 1186. [Abstract] [Full Text] [PDF]
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L. S. Metelitsa, O. V. Naidenko, A. Kant, H.-W. Wu, M. J. Loza, B. Perussia, M. Kronenberg, and R. C. Seeger Human NKT Cells Mediate Antitumor Cytotoxicity Directly by Recognizing Target Cell CD1d with Bound Ligand or Indirectly by Producing IL-2 to Activate NK Cells J. Immunol., September 15, 2001; 167(6): 3114 - 3122. [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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N. Kamada, H. Iijima, K. Kimura, M. Harada, E. Shimizu, S.-i. Motohashi, T. Kawano, H. Shinkai, T. Nakayama, T. Sakai, et al. Crucial amino acid residues of mouse CD1d for glycolipid ligand presentation to V{{alpha}}14 NKT cells Int. Immunol., July 1, 2001; 13(7): 853 - 861. [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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 T. Shiina, A. Ando, Y. Suto, F. Kasai, A. Shigenari, N. Takishima, E. Kikkawa, K. Iwata, Y. Kuwano, Y. Kitamura, et al. Genomic Anatomy of a Premier Major Histocompatibility Complex Paralogous Region on Chromosome 1q21-q22 Genome Res., May 1, 2001; 11(5): 789 - 802. [Abstract] [Full Text]
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S.-H. Park, A. Weiss, K. Benlagha, T. Kyin, L. Teyton, and A. Bendelac The Mouse Cd1d-Restricted Repertoire Is Dominated by a Few Autoreactive T Cell Receptor Families J. Exp. Med., April 16, 2001; 193(8): 893 - 904. [Abstract] [Full Text] [PDF]
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M. J. Smyth, E. Cretney, K. Takeda, R. H. Wiltrout, L. M. Sedger, N. Kayagaki, H. Yagita, and K. Okumura Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (Trail) Contributes to Interferon {gamma}-Dependent Natural Killer Cell Protection from Tumor Metastasis J. Exp. Med., March 19, 2001; 193(6): 661 - 670. [Abstract] [Full Text] [PDF]
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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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M. Kronenberg, O. Naidenko, and F. Koning Right on target: Novel approaches for the direct visualization of CD1-specific T cell responses PNAS, March 13, 2001; 98(6): 2950 - 2952. [Full Text] [PDF]
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 M. del C. Salamone, G. A. Rabinovich, A. K. Mendiguren, G. V. Salamone, and L. Fainboim Activation-induced expression of CD1d antigen on mature T cells J. Leukoc. Biol., February 1, 2001; 69(2): 207 - 214. [Abstract] [Full Text]
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C. Ronet, M. Mempel, N. Thieblemont, A. Lehuen, P. Kourilsky, and G. Gachelin Role of the Complementarity-Determining Region 3 (CDR3) of the TCR-{{beta}} Chains Associated with the V{{alpha}}14 Semi-Invariant TCR {{alpha}}-Chain in the Selection of CD4+ NK T Cells J. Immunol., February 1, 2001; 166(3): 1755 - 1762. [Abstract] [Full Text] [PDF]
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 T. I. Prigozy, O. Naidenko, P. Qasba, D. Elewaut, L. Brossay, A. Khurana, T. Natori, Y. Koezuka, A. Kulkarni, and M. Kronenberg Glycolipid Antigen Processing for Presentation by CD1d Molecules Science, January 26, 2001; 291(5504): 664 - 667. [Abstract] [Full Text]
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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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E. Pal, T. Tabira, T. Kawano, M. Taniguchi, S. Miyake, and T. Yamamura Costimulation-Dependent Modulation of Experimental Autoimmune Encephalomyelitis by Ligand Stimulation of V{{alpha}}14 NK T Cells J. Immunol., January 1, 2001; 166(1): 662 - 668. [Abstract] [Full Text] [PDF]
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K. J. Andrews, A. Ribas, L. H. Butterfield, C. M. Vollmer, F. C. Eilber, V. B. Dissette, S. D. Nelson, P. Shintaku, S. Mekhoubad, T. Nakayama, et al. Adenovirus-Interleukin-12-mediated Tumor Regression in a Murine Hepatocellular Carcinoma Model Is Not Dependent on CD1-restricted Natural Killer T Cells Cancer Res., November 1, 2000; 60(22): 6457 - 6464. [Abstract] [Full Text]
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L. M. Araujo, A. Puel, C. Gouarin, A. Hameg, J.-C. Mevel, Y. Koezuka, J.-F. Bach, D. Mouton, and A. Herbelin NKT lymphocyte ontogeny and function are impaired in low antibody-producer Biozzi mice: gene mapping in the interval-specific congenic strains raised for immunomodulatory genes Int. Immunol., November 1, 2000; 12(11): 1613 - 1622. [Abstract] [Full Text] [PDF]
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A. Hameg, I. Apostolou, M. Leite-de-Moraes, J.-M. Gombert, C. Garcia, Y. Koezuka, J.-F. Bach, and A. Herbelin A Subset of NKT Cells That Lacks the NK1.1 Marker, Expresses CD1d Molecules, and Autopresents the {alpha}-Galactosylceramide Antigen J. Immunol., November 1, 2000; 165(9): 4917 - 4926. [Abstract] [Full Text] [PDF]
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M. C. Leite-de-Moraes, A. Herbelin, C. Gouarin, Y. Koezuka, E. Schneider, and M. Dy Fas/Fas Ligand Interactions Promote Activation-Induced Cell Death of NK T Lymphocytes J. Immunol., October 15, 2000; 165(8): 4367 - 4371. [Abstract] [Full Text] [PDF]
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K. Kakimi, L. G. Guidotti, Y. Koezuka, and F. V. Chisari Natural Killer T Cell Activation Inhibits Hepatitis B Virus Replication in Vivo J. Exp. Med., October 2, 2000; 192(7): 921 - 930. [Abstract] [Full Text] [PDF]
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B. Bonish, D. Jullien, Y. Dutronc, B. B. Huang, R. Modlin, F. M. Spada, S. A. Porcelli, and B. J. Nickoloff Overexpression of CD1d by Keratinocytes in Psoriasis and CD1d-Dependent IFN-{gamma} Production by NK-T Cells J. Immunol., October 1, 2000; 165(7): 4076 - 4085. [Abstract] [Full Text] [PDF]
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J. L. Matsuda, O. V. Naidenko, L. Gapin, T. Nakayama, M. Taniguchi, C.-R. Wang, Y. Koezuka, and M. Kronenberg Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers J. Exp. Med., September 5, 2000; 192(5): 741 - 754. [Abstract] [Full Text] [PDF]
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I. Apostolou, A. Cumano, G. Gachelin, and P. Kourilsky Evidence for Two Subgroups of CD4-CD8- NKT Cells with Distinct TCR{alpha}{beta} Repertoires and Differential Distribution in Lymphoid Tissues J. Immunol., September 1, 2000; 165(5): 2481 - 2490. [Abstract] [Full Text] [PDF]
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N. Burdin, L. Brossay, M. Degano, H. Iijima, M. Gui, I. A. Wilson, and M. Kronenberg Structural requirements for antigen presentation by mouse CD1 PNAS, August 29, 2000; 97(18): 10156 - 10161. [Abstract] [Full Text] [PDF]
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S. Ishihara, M. Nieda, J. Kitayama, T. Osada, T. Yabe, A. Kikuchi, Y. Koezuka, S. A. Porcelli, K. Tadokoro, H. Nagawa, et al. {alpha}-Glycosylceramides Enhance the Antitumor Cytotoxicity of Hepatic Lymphocytes Obtained from Cancer Patients by Activating CD3-CD56+ NK Cells In Vitro J. Immunol., August 1, 2000; 165(3): 1659 - 1664. [Abstract] [Full Text] [PDF]
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