Cd1-Restricted Nk T Cells Protect Nonobese Diabetic Mice from Developing Diabetes

doi:10.1084/jem.194.3.313

Published online 6 August 2001. doi:10.1084/jem.194.3.313

This Article

	Full Text
	Full Text (PDF, 155K)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Wang, B.
	Articles by Wang, C.-R.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Wang, B.
	Articles by Wang, C.-R.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0022-1007/2001/8/313/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 3, August 6, 2001 313-320

Original Article

Cd1-Restricted Nk T Cells Protect Nonobese Diabetic Mice from Developing Diabetes

Bin Wang^a, Yan-Biao Geng^a, and Chyung-Ru Wang^a

^a Gwen Knapp Center for Lupus and Immunology Research, Committee on Immunology, and Department of Pathology, University of Chicago, Chicago, IL 60637
Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, 924 East 57th St., Rm. 412, Chicago, IL 60637-5420.773-702-1576773-702-4725

cwang{at}midway.uchicago.edu

NK T cells are a unique subset of T cells that recognize lipidantigens presented by CD1d. After activation, NK T cells promptlyproduce large amounts of cytokines, which may modulate the upcomingimmune responses. Previous studies have documented an associationbetween decreased numbers of NK T cells and the progressionof some autoimmune diseases, suggesting that NK T cells maycontrol the development of autoimmune diseases. To investigatethe role of NK T cells in autoimmune diabetes, we crossed CD1knockout (CD1KO) mutation onto the nonobese diabetic (NOD) geneticbackground. We found that male CD1KO NOD mice exhibited significantlyhigher incidence and earlier onset of diabetes compared withthe heterozygous controls. The diabetic frequencies in femalemice showed a similar pattern; however, the differences wereless profound between female CD1KO and control mice. Early treatmentof NOD mice with ${alpha}$ -galactosylceramide, a potent NK T cell activator,reduced the severity of autoimmune diabetes in a CD1-dependentmanner. Our results not only suggest a protective role of CD1-restrictedNK T cells in autoimmune diabetes but also reveal a causativelink between the deficiency of NK T cells and the inductionof insulin-dependent diabetes mellitus.

Key Words: CD1 • NK T cells • autoimmunity • diabetes • cytokines

Abbreviations used in this paper: IDDM, insulin-dependent diabetesmellitus; KO, knockout; NOD, nonobese diabetic.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Sille, F. C. M., Boxem, M., Sprengers, D., Veerapen, N., Besra, G., Boes, M. (2009). Distinct Requirements for CD1d Intracellular Transport for Development of V{alpha}14 iNKT Cells. J. Immunol. 183: 1780-1788 [Abstract] [Full Text]
Ueno, A., Wang, J., Cheng, L., Im, J. S., Shi, Y., Porcelli, S. A., Yang, Y. (2008). Enhanced Early Expansion and Maturation of Semi-Invariant NK T Cells Inhibited Autoimmune Pathogenesis in Congenic Nonobese Diabetic Mice. J. Immunol. 181: 6789-6796 [Abstract] [Full Text]
Chen, Y., Akirav, E. M., Chen, W., Henegariu, O., Moser, B., Desai, D., Shen, J. M., Webster, J. C., Andrews, R. C., Mjalli, A. M., Rothlein, R., Schmidt, A. M., Clynes, R., Herold, K. C. (2008). RAGE Ligation Affects T Cell Activation and Controls T Cell Differentiation. J. Immunol. 181: 4272-4278 [Abstract] [Full Text]
Huang, Y., Fugier-Vivier, I. J., Miller, T., Elliott, M. J., Xu, H., Bozulic, L. D., Chilton, P. M., Ildstad, S. T. (2008). Plasmacytoid Precursor Dendritic Cells From NOD Mice Exhibit Impaired Function: Are They a Component of Diabetes Pathogenesis?. Diabetes 57: 2360-2370 [Abstract] [Full Text]
Vallois, D., Gagnerault, M.-C., Avner, P., Rogner, U. C., Boitard, C., Benlagha, K., Herbelin, A., Lepault, F. (2008). Influence of a Non-NK Complex Region of Chromosome 6 on CD4+ Invariant NK T Cell Homeostasis. J. Immunol. 181: 1753-1759 [Abstract] [Full Text]
Tsukamoto, K., Ohtsuji, M., Shiroiwa, W., Lin, Q., Nakamura, K., Tsurui, H., Jiang, Y., Sudo, K., Nishimura, H., Shirai, T., Hirose, S. (2008). Aberrant Genetic Control of Invariant TCR-Bearing NKT Cell Function in New Zealand Mouse Strains: Possible Involvement in Systemic Lupus Erythematosus Pathogenesis. J. Immunol. 180: 4530-4539 [Abstract] [Full Text]
Chen, G., Han, G., Wang, J., Wang, R., Xu, R., Shen, B., Qian, J., Li, Y. (2008). Induction of Active Tolerance and Involvement of CD1d-Restricted Natural Killer T Cells in Anti-CD3 F(ab')2 Treatment-Reversed New-Onset Diabetes in Nonobese Diabetic Mice. Am. J. Pathol. 172: 972-979 [Abstract] [Full Text]
Hussain, S., Delovitch, T. L. (2007). Intravenous Transfusion of BCR-Activated B Cells Protects NOD Mice from Type 1 Diabetes in an IL-10-Dependent Manner. J. Immunol. 179: 7225-7232 [Abstract] [Full Text]
Novak, J., Beaudoin, L., Park, S., Griseri, T., Teyton, L., Bendelac, A., Lehuen, A. (2007). Prevention of Type 1 Diabetes by Invariant NKT Cells Is Independent of Peripheral CD1d Expression. J. Immunol. 178: 1332-1340 [Abstract] [Full Text]
Forestier, C., Takaki, T., Molano, A., Im, J. S., Baine, I., Jerud, E. S., Illarionov, P., Ndonye, R., Howell, A. R., Santamaria, P., Besra, G. S., DiLorenzo, T. P., Porcelli, S. A. (2007). Improved Outcomes in NOD Mice Treated with a Novel Th2 Cytokine-Biasing NKT Cell Activator. J. Immunol. 178: 1415-1425 [Abstract] [Full Text]
Ly, D., Mi, Q.-S., Hussain, S., Delovitch, T. L. (2006). Protection from Type 1 Diabetes by Invariant NK T Cells Requires the Activity of CD4+CD25+ Regulatory T Cells. J. Immunol. 177: 3695-3704 [Abstract] [Full Text]
Rocha-Campos, A.-C., Melki, R., Zhu, R., Deruytter, N., Damotte, D., Dy, M., Herbelin, A., Garchon, H.-J. (2006). Genetic and Functional Analysis of the Nkt1 Locus Using Congenic NOD Mice: Improved V{alpha}14-NKT Cell Performance but Failure to Protect Against Type 1 Diabetes.. Diabetes 55: 1163-1170 [Abstract] [Full Text]
Akbari, O., Faul, J. L., Hoyte, E. G., Berry, G. J., Wahlstrom, J., Kronenberg, M., DeKruyff, R. H., Umetsu, D. T. (2006). CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma.. NEJM 354: 1117-1129 [Abstract] [Full Text]
Cain, J. A., Smith, J. A., Ondr, J. K., Wang, B., Katz, J. D. (2006). NKT Cells and IFN-{gamma} Establish the Regulatory Environment for the Control of Diabetogenic T Cells in the Nonobese Diabetic Mouse. J. Immunol. 176: 1645-1654 [Abstract] [Full Text]
Kent, S. C., Chen, Y., Clemmings, S. M., Viglietta, V., Kenyon, N. S., Ricordi, C., Hering, B., Hafler, D. A. (2005). Loss of IL-4 Secretion from Human Type 1a Diabetic Pancreatic Draining Lymph Node NKT Cells. J. Immunol. 175: 4458-4464 [Abstract] [Full Text]
Uldrich, A. P., Crowe, N. Y., Kyparissoudis, K., Pellicci, D. G., Zhan, Y., Lew, A. M., Bouillet, P., Strasser, A., Smyth, M. J., Godfrey, D. I. (2005). NKT Cell Stimulation with Glycolipid Antigen In Vivo: Costimulation-Dependent Expansion, Bim-Dependent Contraction, and Hyporesponsiveness to Further Antigenic Challenge. J. Immunol. 175: 3092-3101 [Abstract] [Full Text]
Dougan, S. K., Salas, A., Rava, P., Agyemang, A., Kaser, A., Morrison, J., Khurana, A., Kronenberg, M., Johnson, C., Exley, M., Hussain, M. M., Blumberg, R. S. (2005). Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells. JEM 202: 529-539 [Abstract] [Full Text]
Griseri, T., Beaudoin, L., Novak, J., Mars, L. T., Lepault, F., Liblau, R., Lehuen, A. (2005). Invariant NKT Cells Exacerbate Type 1 Diabetes Induced by CD8 T Cells. J. Immunol. 175: 2091-2101 [Abstract] [Full Text]
Geng, Y., Laslo, P., Barton, K., Wang, C.-R. (2005). Transcriptional Regulation of CD1D1 by Ets Family Transcription Factors. J. Immunol. 175: 1022-1029 [Abstract] [Full Text]
Ajuebor, M. N., Aspinall, A. I., Zhou, F., Le, T., Yang, Y., Urbanski, S. J., Sidobre, S., Kronenberg, M., Hogaboam, C. M., Swain, M. G. (2005). Lack of Chemokine Receptor CCR5 Promotes Murine Fulminant Liver Failure by Preventing the Apoptosis of Activated CD1d-Restricted NKT Cells. J. Immunol. 174: 8027-8037 [Abstract] [Full Text]
Yu, K. O. A., Im, J. S., Molano, A., Dutronc, Y., Illarionov, P. A., Forestier, C., Fujiwara, N., Arias, I., Miyake, S., Yamamura, T., Chang, Y.-T., Besra, G. S., Porcelli, S. A. (2005). Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of {alpha}-galactosylceramides. Proc. Natl. Acad. Sci. USA 102: 3383-3388 [Abstract] [Full Text]
Chen, Y.-G., Choisy-Rossi, C.-M., Holl, T. M., Chapman, H. D., Besra, G. S., Porcelli, S. A., Shaffer, D. J., Roopenian, D., Wilson, S. B., Serreze, D. V. (2005). Activated NKT Cells Inhibit Autoimmune Diabetes through Tolerogenic Recruitment of Dendritic Cells to Pancreatic Lymph Nodes. J. Immunol. 174: 1196-1204 [Abstract] [Full Text]
Duthie, M. S., Kahn, M., White, M., Kapur, R. P., Kahn, S. J. (2005). Critical Proinflammatory and Anti-Inflammatory Functions of Different Subsets of CD1d-Restricted Natural Killer T Cells during Trypanosoma cruzi Infection. Infect. Immun. 73: 181-192 [Abstract] [Full Text]
Bach, J.-F., Bendelac, A., Brenner, M. B., Cantor, H., De Libero, G., Kronenberg, M., Lanier, L. L., Raulet, D. H., Shlomchik, M. J., von Herrath, M. G. (2004). The Role of Innate Immunity in Autoimmunity. JEM 200: 1527-1531 [Abstract] [Full Text]
Machen, J., Harnaha, J., Lakomy, R., Styche, A., Trucco, M., Giannoukakis, N. (2004). Antisense Oligonucleotides Down-Regulating Costimulation Confer Diabetes-Preventive Properties to Nonobese Diabetic Mouse Dendritic Cells. J. Immunol. 173: 4331-4341 [Abstract] [Full Text]
Van Rhijn, I., Young, D. C., Im, J. S., Levery, S. B., Illarionov, P. A., Besra, G. S., Porcelli, S. A., Gumperz, J., Cheng, T.-Y., Moody, D. B. (2004). CD1d-restricted T cell activation by nonlipidic small molecules. Proc. Natl. Acad. Sci. USA 101: 13578-13583 [Abstract] [Full Text]
Duarte, N., Stenstrom, M., Campino, S., Bergman, M.-L., Lundholm, M., Holmberg, D., Cardell, S. L. (2004). Prevention of Diabetes in Nonobese Diabetic Mice Mediated by CD1d-Restricted Nonclassical NKT Cells. J. Immunol. 173: 3112-3118 [Abstract] [Full Text]
Pearson, T., Weiser, P., Markees, T. G., Serreze, D. V., Wicker, L. S., Peterson, L. B., Cumisky, A.-M., Shultz, L. D., Mordes, J. P., Rossini, A. A., Greiner, D. L. (2004). Islet Allograft Survival Induced by Costimulation Blockade in NOD Mice Is Controlled by Allelic Variants of Idd3. Diabetes 53: 1972-1978 [Abstract] [Full Text]
Nagayama, Y., Watanabe, K., Niwa, M., McLachlan, S. M., Rapoport, B. (2004). Schistosoma mansoni and {alpha}-Galactosylceramide: Prophylactic Effect of Th1 Immune Suppression in a Mouse Model of Graves' Hyperthyroidism. J. Immunol. 173: 2167-2173 [Abstract] [Full Text]
Fischer, K., Scotet, E., Niemeyer, M., Koebernick, H., Zerrahn, J., Maillet, S., Hurwitz, R., Kursar, M., Bonneville, M., Kaufmann, S. H. E., Schaible, U. E. (2004). Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells. Proc. Natl. Acad. Sci. USA 101: 10685-10690 [Abstract] [Full Text]
Mi, Q.-S., Ly, D., Zucker, P., McGarry, M., Delovitch, T. L. (2004). Interleukin-4 but not Interleukin-10 Protects Against Spontaneous and Recurrent Type 1 Diabetes by Activated CD1d-Restricted Invariant Natural Killer T-Cells. Diabetes 53: 1303-1310 [Abstract] [Full Text]
Rauch, J., Gumperz, J., Robinson, C., Skold, M., Roy, C., Young, D. C., Lafleur, M., Moody, D. B., Brenner, M. B., Costello, C. E., Behar, S. M. (2003). Structural Features of the Acyl Chain Determine Self-phospholipid Antigen Recognition by a CD1d-restricted Invariant NKT (iNKT) Cell. J. Biol. Chem. 278: 47508-47515 [Abstract] [Full Text]
Xu, H., Chun, T., Colmone, A., Nguyen, H., Wang, C.-R. (2003). Expression of CD1d Under the Control of a MHC Class Ia Promoter Skews the Development of NKT Cells, But Not CD8+ T Cells. J. Immunol. 171: 4105-4112 [Abstract] [Full Text]
Yang, J.-Q., Saxena, V., Xu, H., Van Kaer, L., Wang, C.-R., Singh, R. R. (2003). Repeated {alpha}-Galactosylceramide Administration Results in Expansion of NK T Cells and Alleviates Inflammatory Dermatitis in MRL-lpr/lpr Mice. J. Immunol. 171: 4439-4446 [Abstract] [Full Text]
Yang, J.-Q., Singh, A. K., Wilson, M. T., Satoh, M., Stanic, A. K., Park, J.-J., Hong, S., Gadola, S. D., Mizutani, A., Kakumanu, S. R., Reeves, W. H., Cerundolo, V., Joyce, S., Van Kaer, L., Singh, R. R. (2003). Immunoregulatory Role of CD1d in the Hydrocarbon Oil-Induced Model of Lupus Nephritis. J. Immunol. 171: 2142-2153 [Abstract] [Full Text]
Mi, Q.-S., Ly, D., Lamhamedi-Cherradi, S.-E., Salojin, K. V., Zhou, L., Grattan, M., Meagher, C., Zucker, P., Chen, Y. H., Nagle, J., Taub, D., Delovitch, T. L. (2003). Blockade of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Exacerbates Type 1 Diabetes in NOD Mice. Diabetes 52: 1967-1975 [Abstract] [Full Text]
Fujii, S.-i., Shimizu, K., Smith, C., Bonifaz, L., Steinman, R. M. (2003). Activation of Natural Killer T Cells by {alpha}-Galactosylceramide Rapidly Induces the Full Maturation of Dendritic Cells In Vivo and Thereby Acts as an Adjuvant for Combined CD4 and CD8 T Cell Immunity to a Coadministered Protein. JEM 198: 267-279 [Abstract] [Full Text]
Matsuki, N., Stanic, A. K., Embers, M. E., Van Kaer, L., Morel, L., Joyce, S. (2003). Genetic Dissection of V{alpha}14J{alpha}18 Natural T Cell Number and Function in Autoimmune-Prone Mice. J. Immunol. 170: 5429-5437 [Abstract] [Full Text]
Chun, T., Page, M. J., Gapin, L., Matsuda, J. L., Xu, H., Nguyen, H., Kang, H.-S., Stanic, A. K., Joyce, S., Koltun, W. A., Chorney, M. J., Kronenberg, M., Wang, C.-R. (2003). CD1d-expressing Dendritic Cells but Not Thymic Epithelial Cells Can Mediate Negative Selection of NKT Cells. JEM 197: 907-918 [Abstract] [Full Text]
Araki, M., Kondo, T., Gumperz, J. E., Brenner, M. B., Miyake, S., Yamamura, T. (2003). Th2 bias of CD4+ NKT cells derived from multiple sclerosis in remission. Int Immunol 15: 279-288 [Abstract] [Full Text]
Pearson, T., Markees, T. G., Wicker, L. S., Serreze, D. V., Peterson, L. B., Mordes, J. P., Rossini, A. A., Greiner, D. L. (2003). NOD Congenic Mice Genetically Protected From Autoimmune Diabetes Remain Resistant to Transplantation Tolerance Induction. Diabetes 52: 321-326 [Abstract] [Full Text]
Kanagawa, O., Militech, A., Vaupel, B. A. (2002). Regulation of Diabetes Development by Regulatory T Cells in Pancreatic Islet Antigen-Specific TCR Transgenic Nonobese Diabetic Mice. J. Immunol. 168: 6159-6164 [Abstract] [Full Text]
Prasad, S. J., Goodnow, C. C. (2002). Cell-intrinsic effects of non-MHC NOD genes on dendritic cell generation in vivo. Int Immunol 14: 677-684 [Abstract] [Full Text]
Bendelac, A., Medzhitov, R. (2002). Adjuvants of Immunity: Harnessing Innate Immunity to Promote Adaptive Immunity. JEM 195: F19-F23 [Full Text]
Jahng, A. W., Maricic, I., Pedersen, B., Burdin, N., Naidenko, O., Kronenberg, M., Koezuka, Y., Kumar, V. (2001). Activation of Natural Killer T Cells Potentiates or Prevents Experimental Autoimmune Encephalomyelitis. JEM 194: 1789-1799 [Abstract] [Full Text]
Singh, A. K., Wilson, M. T., Hong, S., Olivares-Villagomez, D., Du, C., Stanic, A. K., Joyce, S., Sriram, S., Koezuka, Y., Van Kaer, L. (2001). Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis. JEM 194: 1801-1811 [Abstract] [Full Text]
Naumov, Y. N., Bahjat, K. S., Gausling, R., Abraham, R., Exley, M. A., Koezuka, Y., Balk, S. B., Strominger, J. L., Clare-Salzer, M., Wilson, S. B. (2001). Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets. Proc. Natl. Acad. Sci. USA 10.1073/pnas.251531798v1 [Abstract] [Full Text]
Naumov, Y. N., Bahjat, K. S., Gausling, R., Abraham, R., Exley, M. A., Koezuka, Y., Balk, S. B., Strominger, J. L., Clare-Salzer, M., Wilson, S. B. (2001). Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets. Proc. Natl. Acad. Sci. USA 98: 13838-13843 [Abstract] [Full Text]
Pellicci, D. G., Hammond, K. J.L., Uldrich, A. P., Baxter, A. G., Smyth, M. J., Godfrey, D. I. (2002). A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1-CD4+ CD1d-dependent Precursor Stage. JEM 195: 835-844 [Abstract] [Full Text]