A Defect in Interleukin 12-Induced Activation and Interferon {gamma} Secretion of Peripheral Natural Killer T Cells in Nonobese Diabetic Mice Suggests New Pathogenic Mechanisms for Insulin-Dependent Diabetes Mellitus

doi:10.1084/jem.190.7.963

This Article

	Full Text
	Full Text (PDF, 119K)
	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 Falcone, M.
	Articles by Sarvetnick, N.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Falcone, M.
	Articles by Sarvetnick, N.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0022-1007/1999/10/963/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 7, October 4, 1999 963-972

Original Article

A Defect in Interleukin 12–Induced Activation and Interferon ${gamma}$ Secretion of Peripheral Natural Killer T Cells in Nonobese Diabetic Mice Suggests New Pathogenic Mechanisms for Insulin-Dependent Diabetes Mellitus

Marika Falcone^a, Brian Yeung^a, Lee Tucker^a, Enrique Rodriguez^a, and Nora Sarvetnick^a

^a Department of Immunology, The Scripps Research Institute, La Jolla, California 92037
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037.858-784-9083858-784-9066

noras{at}scripps.edu

The function of natural killer T (NKT) cells in the immune systemhas yet to be determined. There is some evidence that theirdefect is associated with autoimmunity, but it is still unclearhow they play a role in regulating the pathogenesis of T cell–mediatedautoimmune diseases. It was originally proposed that NKT cellscould control autoimmunity by shifting the cytokine profileof autoimmune T cells toward a protective T helper 2 cell (Th2)type. However, it is now clear that the major function of NKTcells in the immune system is not related to their interleukin(IL)-4 secretion. In fact, NKT cells mainly secrete interferon(IFN)- ${gamma}$ and, activated in the presence of IL-12, acquire a stronginflammatory phenotype and cytotoxic function.

Key Words: natural killer T cells • interferon ${gamma}$ • interleukin 4 • autoimmunity • regulatory cells

1used in this paper: EAE, experimental autoimmune encephalomyelitis;IDDM, insulin-dependent diabetes mellitus; 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:

Driver, J. P., Scheuplein, F., Chen, Y.-G., Grier, A. E., Wilson, S. B., Serreze, D. V. (2010). Invariant Natural Killer T-Cell Control of Type 1 Diabetes: A Dendritic Cell Genetic Decision of a Silver Bullet or Russian Roulette. Diabetes 59: 423-432 [Abstract] [Full Text]
Baev, D. V., Caielli, S., Ronchi, F., Coccia, M., Facciotti, F., Nichols, K. E., Falcone, M. (2008). Impaired SLAM-SLAM Homotypic Interaction between Invariant NKT Cells and Dendritic Cells Affects Differentiation of IL-4/IL-10-Secreting NKT2 Cells in Nonobese Diabetic Mice. J. Immunol. 181: 869-877 [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]
Zhang, C., Todorov, I., Lin, C.-L., Atkinson, M., Kandeel, F., Forman, S., Zeng, D. (2007). Elimination of insulitis and augmentation of islet beta cell regeneration via induction of chimerism in overtly diabetic NOD mice. Proc. Natl. Acad. Sci. USA 104: 2337-2342 [Abstract] [Full Text]
Jiang, H., Chess, L. (2006). Regulation of immune responses by T cells.. NEJM 354: 1166-1176 [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]
Bezbradica, J. S., Stanic, A. K., Matsuki, N., Bour-Jordan, H., Bluestone, J. A., Thomas, J. W., Unutmaz, D., Van Kaer, L., Joyce, S. (2005). Distinct Roles of Dendritic Cells and B Cells in Va14Ja18 Natural T Cell Activation In Vivo. J. Immunol. 174: 4696-4705 [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]
Matsumoto, G., Kubota, E., Omi, Y., Lee, U., Penninger, J. M. (2004). Essential Role of LFA-1 in Activating Th2-Like Responses by {alpha}-Galactosylceramide-Activated NKT Cells. J. Immunol. 173: 4976-4984 [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]
Falcone, M., Facciotti, F., Ghidoli, N., Monti, P., Olivieri, S., Zaccagnino, L., Bonifacio, E., Casorati, G., Sanvito, F., Sarvetnick, N. (2004). Up-Regulation of CD1d Expression Restores the Immunoregulatory Function of NKT Cells and Prevents Autoimmune Diabetes in Nonobese Diabetic Mice. J. Immunol. 172: 5908-5916 [Abstract] [Full Text]
Ortaldo, J. R., Young, H. A., Winkler-Pickett, R. T., Bere, E. W. Jr., Murphy, W. J., Wiltrout, R. H. (2004). Dissociation of NKT Stimulation, Cytokine Induction, and NK Activation In Vivo by the Use of Distinct TCR-Binding Ceramides. J. Immunol. 172: 943-953 [Abstract] [Full Text]
Matsuda, J. L., Gapin, L., Baron, J. L., Sidobre, S., Stetson, D. B., Mohrs, M., Locksley, R. M., Kronenberg, M. (2003). Mouse V{alpha}14i natural killer T cells are resistant to cytokine polarization in vivo. Proc. Natl. Acad. Sci. USA 100: 8395-8400 [Abstract] [Full Text]
Mars, L. T., Laloux, V., Goude, K., Desbois, S., Saoudi, A., Van Kaer, L., Lassmann, H., Herbelin, A., Lehuen, A., Liblau, R. S. (2002). Cutting Edge: V{alpha}14-J{alpha}281 NKT Cells Naturally Regulate Experimental Autoimmune Encephalomyelitis in Nonobese Diabetic Mice. J. Immunol. 168: 6007-6011 [Abstract] [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]
Yang, Y., Bao, M., Yoon, J.-W. (2001). 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 50: 2691-2699 [Abstract] [Full Text]
Wang, B., Geng, Y.-B., Wang, C.-R. (2001). Cd1-Restricted Nk T Cells Protect Nonobese Diabetic Mice from Developing Diabetes. JEM 194: 313-320 [Abstract] [Full Text]
Hammond, K. J. L., Pellicci, D. G., Poulton, L. D., Naidenko, O. V., Scalzo, A. A., Baxter, A. G., Godfrey, D. I. (2001). CD1d-Restricted NKT Cells: An Interstrain Comparison. J. Immunol. 167: 1164-1173 [Abstract] [Full Text]
Weaver, D. J. Jr., Poligone, B., Bui, T., Abdel-Motal, U. M., Baldwin, A. S. Jr., Tisch, R. (2001). Dendritic Cells from Nonobese Diabetic Mice Exhibit a Defect in NF-{kappa}B Regulation Due to a Hyperactive I{kappa}B Kinase. J. Immunol. 167: 1461-1468 [Abstract] [Full Text]
Cunningham, M. W. (2001). Cardiac Myosin and the TH1/TH2 Paradigm in Autoimmune Myocarditis. Am. J. Pathol. 159: 5-12 [Full Text]
Shi, F.-D., Flodstrom, M., Balasa, B., Kim, S. H., Van Gunst, K., Strominger, J. L., Wilson, S. B., Sarvetnick, N. (2001). Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse. Proc. Natl. Acad. Sci. USA 98: 6777-6782 [Abstract] [Full Text]
Laloux, V., Beaudoin, L., Jeske, D., Carnaud, C., Lehuen, A. (2001). 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. 166: 3749-3756 [Abstract] [Full Text]
Carnaud, C., Gombert, J.-M., Donnars, O., Garchon, H.-J., Herbelin, A. (2001). Protection Against Diabetes and Improved NK/NKT Cell Performance in NOD.NK1.1 Mice Congenic at the NK Complex. J. Immunol. 166: 2404-2411 [Abstract] [Full Text]
Seino, K.-i., Fukao, K., Muramoto, K., Yanagisawa, K., Takada, Y., Kakuta, S., Iwakura, Y., Van Kaer, L., Takeda, K., Nakayama, T., Taniguchi, M., Bashuda, H., Yagita, H., Okumura, K. (2001). Requirement for natural killer T (NKT) cells in the induction of allograft tolerance. Proc. Natl. Acad. Sci. USA 10.1073/pnas.041608298v1 [Abstract] [Full Text]
Pal, E., Tabira, T., Kawano, T., Taniguchi, M., Miyake, S., Yamamura, T. (2001). Costimulation-Dependent Modulation of Experimental Autoimmune Encephalomyelitis by Ligand Stimulation of V{{alpha}}14 NK T Cells. J. Immunol. 166: 662-668 [Abstract] [Full Text]
Yang, O. O., Racke, F. K., Nguyen, P. T., Gausling, R., Severino, M. E., Horton, H. F., Byrne, M. C., Strominger, J. L., Wilson, S. B. (2000). CD1d on Myeloid Dendritic Cells Stimulates Cytokine Secretion from and Cytolytic Activity of V{alpha}24J{alpha}Q T Cells: A Feedback Mechanism for Immune Regulation. J. Immunol. 165: 3756-3762 [Abstract] [Full Text]
Matsuda, J. L., Naidenko, O. V., Gapin, L., Nakayama, T., Taniguchi, M., Wang, C.-R., Koezuka, Y., Kronenberg, M. (2000). Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers. JEM 192: 741-754 [Abstract] [Full Text]
Apostolou, I., Cumano, A., Gachelin, G., Kourilsky, P. (2000). Evidence for Two Subgroups of CD4-CD8- NKT Cells with Distinct TCR{alpha}{beta} Repertoires and Differential Distribution in Lymphoid Tissues. J. Immunol. 165: 2481-2490 [Abstract] [Full Text]
Joyce, S. (2000). Natural T cells: Cranking up the immune system by prompt cytokine secretion. Proc. Natl. Acad. Sci. USA 97: 6933-6935 [Full Text]
Walunas, T. L., Wang, B., Wang, C.-R., Leiden, J. M. (2000). Cutting Edge: The Ets1 Transcription Factor Is Required for the Development of NK T Cells in Mice. J. Immunol. 164: 2857-2860 [Abstract] [Full Text]
Seino, K.-i., Fukao, K., Muramoto, K., Yanagisawa, K., Takada, Y., Kakuta, S., Iwakura, Y., Van Kaer, L., Takeda, K., Nakayama, T., Taniguchi, M., Bashuda, H., Yagita, H., Okumura, K. (2001). Requirement for natural killer T (NKT) cells in the induction of allograft tolerance. Proc. Natl. Acad. Sci. USA 98: 2577-2581 [Abstract] [Full Text]
Wilson, S. B., Kent, S. C., Horton, H. F., Hill, A. A., Bollyky, P. L., Hafler, D. A., Strominger, J. L., Byrne, M. C. (2000). Multiple differences in gene expression in regulatory Valpha 24Jalpha Q T cells from identical twins discordant for type I diabetes. Proc. Natl. Acad. Sci. USA 97: 7411-7416 [Abstract] [Full Text]
Matsuda, J. L., Gapin, L., Fazilleau, N., Warren, K., Naidenko, O. V., Kronenberg, M. (2001). Natural killer T cells reactive to a single glycolipid exhibit a highly diverse T cell receptor beta repertoire and small clone size. Proc. Natl. Acad. Sci. USA 98: 12636-12641 [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]