Interleukin 12 administration induces T helper type 1 cells and accelerates autoimmune diabetes in NOD mice

doi:10.1084/jem.181.2.817

This Article

	Full Text (PDF, 2848K)
	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 Trembleau, S.
	Articles by Adorini, L.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Trembleau, S.
	Articles by Adorini, L.


Social Bookmarking

	What's this?

ARTICLES

Interleukin 12 administration induces T helper type 1 cells and accelerates autoimmune diabetes in NOD mice

S Trembleau, G Penna, E Bosi, A Mortara, MK Gately and L Adorini
Roche Milano Ricerche, Italy.

T cells play a major role in the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. Administration of interleukin 12 (IL-12), a key cytokine which guides the development of T helper type 1 (Th1) CD4+ T cells, induces rapid onset of IDDM in NOD, but not in BALB/c mice. Histologically, IL-12 administration induces massive infiltration of lymphoid cells, mostly T cells, in the pancreatic islets of NOD mice. CD4+ pancreas-infiltrating T cells, after activation by insolubilized anti T cell receptor antibody, secrete high levels of interferon gamma and low levels of IL- 4. Therefore, IL-12 administration accelerates IDDM development in genetically susceptible NOD mice, and this correlates with increased Th1 cytokine production by islet-infiltrating cells. These results hold implications for the pathogenesis, and possibly for the therapy of IDDM and of other Th1 cell-mediated autoimmune diseases.
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:

Esensten, J. H., Lee, M. R., Glimcher, L. H., Bluestone, J. A. (2009). T-bet-Deficient NOD Mice Are Protected from Diabetes Due to Defects in Both T Cell and Innate Immune System Function. J. Immunol. 183: 75-82 [Abstract] [Full Text]
Maier, L. M., Howlett, S. K., Rainbow, K. M., Clark, J., Howson, J. M. M., Todd, J. A., Wicker, L. S. (2008). NKG2D-RAE-1 Receptor-Ligand Variation Does Not Account for the NK Cell Defect in Nonobese Diabetic Mice. J. Immunol. 181: 7073-7080 [Abstract] [Full Text]
Wildenberg, M. E., van Helden-Meeuwsen, C. G., van de Merwe, J. P., Moreno, C., Drexhage, H. A., Versnel, M. A. (2008). Lack of CCR5 on dendritic cells promotes a proinflammatory environment in submandibular glands of the NOD mouse. J. Leukoc. Biol. 83: 1194-1200 [Abstract] [Full Text]
Irie, J., Reck, B., Wu, Y., Wicker, L. S., Howlett, S., Rainbow, D., Feingold, E., Ridgway, W. M. (2008). Genome-Wide Microarray Expression Analysis of CD4+ T Cells from Nonobese Diabetic Congenic Mice Identifies Cd55 (Daf1) and Acadl as Candidate Genes for Type 1 Diabetes. J. Immunol. 180: 1071-1079 [Abstract] [Full Text]
Enzler, T., Gillessen, S., Dougan, M., Allison, J. P., Neuberg, D., Oble, D. A., Mihm, M., Dranoff, G. (2007). Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of {beta} cells. Blood 110: 954-961 [Abstract] [Full Text]
Saito, S., Matsuura, M., Hirai, Y. (2006). Regulation of Lipopolysaccharide-Induced Interleukin-12 Production by Activation of Repressor Element GA-12 through Hyperactivation of the ERK Pathway.. CVI 13: 876-883 [Abstract] [Full Text]
Fahey, A. J., Robins, R. A., Kindle, K. B., Heery, D. M., Constantinescu, C. S. (2006). Effects of glucocorticoids on STAT4 activation in human T cells are stimulus-dependent. J. Leukoc. Biol. 80: 133-144 [Abstract] [Full Text]
Boyton, R. J., Davies, S., Marden, C., Fantino, C., Reynolds, C., Portugal, K., Dewchand, H., Altmann, D. M. (2005). Stat4-null non-obese diabetic mice: protection from diabetes and experimental allergic encephalomyelitis, but with concomitant epitope spread. Int Immunol 17: 1157-1165 [Abstract] [Full Text]
You, S., Belghith, M., Cobbold, S., Alyanakian, M.-A., Gouarin, C., Barriot, S., Garcia, C., Waldmann, H., Bach, J.-F., Chatenoud, L. (2005). Autoimmune Diabetes Onset Results From Qualitative Rather Than Quantitative Age-Dependent Changes in Pathogenic T-Cells. Diabetes 54: 1415-1422 [Abstract] [Full Text]
Zheng, S.-J., Lamhamedi-Cherradi, S.-E., Wang, P., Xu, L., Chen, Y. H. (2005). Tumor Suppressor p53 Inhibits Autoimmune Inflammation and Macrophage Function. Diabetes 54: 1423-1428 [Abstract] [Full Text]
Zipris, D., Lien, E., Xie, J. X., Greiner, D. L., Mordes, J. P., Rossini, A. A. (2005). TLR Activation Synergizes with Kilham Rat Virus Infection to Induce Diabetes in BBDR Rats. J. Immunol. 174: 131-142 [Abstract] [Full Text]
Martinez-Soria, E., Ibnou-Zekri, N., Iwamoto, M., Santiago-Raber, M.-L., Kikuchi, S., Kosco-Vilbois, M., Izui, S. (2004). Epitope-Dependent Inhibition of T Cell Activation by the Ea Transgene: An Explanation for Transgene-Mediated Protection from Murine Lupus. J. Immunol. 173: 2842-2848 [Abstract] [Full Text]
Bergholdt, R, Ghandil, P, Johannesen, J, Kristiansen, O P, Kockum, I, Luthman, H, Ronningen, K S, Nerup, J, Julier, C, Pociot, F (2004). Genetic and functional evaluation of an interleukin-12 polymorphism (IDDM18) in families with type 1 diabetes. J. Med. Genet. 41: e39-e39 [Full Text]
Zhou, H., Xiong, H., Li, H., Plevy, S. E., Walden, P. D., Sassaroli, M., Prestwich, G. D., Unkeless, J. C. (2004). Microtubule-Associated Serine/Threonine Kinase-205 kDa and Fc{gamma} Receptor Control IL-12 p40 Synthesis and NF-{kappa}B Activation. J. Immunol. 172: 2559-2568 [Abstract] [Full Text]
Morrison, A. C., Wilson, C. B., Ray, M., Correll, P. H. (2004). Macrophage-Stimulating Protein, the Ligand for the Stem Cell-Derived Tyrosine Kinase/RON Receptor Tyrosine Kinase, Inhibits IL-12 Production by Primary Peritoneal Macrophages Stimulated with IFN-{gamma} and Lipopolysaccharide. J. Immunol. 172: 1825-1832 [Abstract] [Full Text]
Oleszak, E. L., Chang, J. R., Friedman, H., Katsetos, C. D., Platsoucas, C. D. (2004). Theiler's Virus Infection: a Model for Multiple Sclerosis. Clin. Microbiol. Rev. 17: 174-207 [Abstract] [Full Text]
Oikawa, Y., Shimada, A., Kasuga, A., Morimoto, J., Osaki, T., Tahara, H., Miyazaki, T., Tashiro, F., Yamato, E., Miyazaki, J.-i., Saruta, T. (2003). Systemic Administration of IL-18 Promotes Diabetes Development in Young Nonobese Diabetic Mice. J. Immunol. 171: 5865-5875 [Abstract] [Full Text]
Gregori, S., Giarratana, N., Smiroldo, S., Adorini, L. (2003). Dynamics of Pathogenic and Suppressor T Cells in Autoimmune Diabetes Development. J. Immunol. 171: 4040-4047 [Abstract] [Full Text]
Shaw, M. H., Boyartchuk, V., Wong, S., Karaghiosoff, M., Ragimbeau, J., Pellegrini, S., Muller, M., Dietrich, W. F., Yap, G. S. (2003). A natural mutation in the Tyk2 pseudokinase domain underlies altered susceptibility of B10.Q/J mice to infection and autoimmunity. Proc. Natl. Acad. Sci. USA 100: 11594-11599 [Abstract] [Full Text]
Trembleau, S., Penna, G., Gregori, S., Giarratana, N., Adorini, L. (2003). IL-12 Administration Accelerates Autoimmune Diabetes in Both Wild-Type and IFN-{gamma}-Deficient Nonobese Diabetic Mice, Revealing Pathogenic and Protective Effects of IL-12-Induced IFN-{gamma}. J. Immunol. 170: 5491-5501 [Abstract] [Full Text]
Sugerman, P.B., Savage, N.W., Walsh, L.J., Zhao, Z.Z., Zhou, X.J., Khan, A., Seymour, G.J., Bigby, M. (2002). THE PATHOGENESIS OF ORAL LICHEN PLANUS. CROBM 13: 350-365 [Abstract] [Full Text]
Davoodi-Semiromi, A., Yang, J. J., She, J.-X. (2002). IL-12p40 Is Associated With Type 1 Diabetes in Caucasian-American Families. Diabetes 51: 2334-2336 [Abstract] [Full Text]
Gregori, S., Giarratana, N., Smiroldo, S., Uskokovic, M., Adorini, L. (2002). A 1{alpha},25-Dihydroxyvitamin D3 Analog Enhances Regulatory T-Cells and Arrests Autoimmune Diabetes in NOD Mice. Diabetes 51: 1367-1374 [Abstract] [Full Text]
Raju, K., Rabinovich, B. A., Radvanyi, L. G., Spaner, D., Miller, R. G. (2001). A central role for IL-2 in fate determination of mature T cells--I: role in determining the Th1/Th2 profile in primary T cell cultures. Int Immunol 13: 1453-1459 [Abstract] [Full Text]
Kollet, J., Witek, C., Gentry, J. D., Liu, X., Schwartzbach, S. D., Petro, T. M. (2001). Deletional Analysis of the Murine IL-12 p35 Promoter Comparing IFN-{gamma} and Lipopolysaccharide Stimulation. J. Immunol. 167: 5653-5663 [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]
Trembleau, S., Gregori, S., Penna, G., Gorny, I., Adorini, L. (2001). IL-12 Administration Reveals Diabetogenic T Cells in Genetically Resistant I-E{alpha}-Transgenic Nonobese Diabetic Mice: Resistance to Autoimmune Diabetes Is Associated with Binding of E{alpha}-Derived Peptides to the I-Ag7 Molecule. J. Immunol. 167: 4104-4114 [Abstract] [Full Text]
Costa, G. L., Sandora, M. R., Nakajima, A., Nguyen, E. V., Taylor-Edwards, C., Slavin, A. J., Contag, C. H., Fathman, C. G., Benson, J. M. (2001). Adoptive Immunotherapy of Experimental Autoimmune Encephalomyelitis Via T Cell Delivery of the IL-12 p40 Subunit. J. Immunol. 167: 2379-2387 [Abstract] [Full Text]
Koarada, S., Wu, Y., Ridgway, W. M. (2001). Increased Entry into the IFN-{gamma} Effector Pathway by CD4+ T Cells Selected by I-Ag7 on a Nonobese Diabetic Versus C57BL/6 Genetic Background. J. Immunol. 167: 1693-1702 [Abstract] [Full Text]
Chen, K., Wei, Y., Sharp, G. C., Braley-Mullen, H. (2001). Induction of Experimental Autoimmune Thyroiditis in IL-12-/- Mice. J. Immunol. 167: 1720-1727 [Abstract] [Full Text]
Grazia Cappiello, M., Sutterwala, F. S., Trinchieri, G., Mosser, D. M., Ma, X. (2001). Suppression of IL-12 Transcription in Macrophages Following Fc{{gamma}} Receptor Ligation. J. Immunol. 166: 4498-4506 [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]
Pauza, M. E., Nguyen, A., Wolfe, T., Ho, I-C., Glimcher, L. H., von Herrath, M., Lo, D. (2001). Variable Effects of Transgenic c-Maf on Autoimmune Diabetes. Diabetes 50: 39-46 [Abstract] [Full Text]
Trembleau, S., Penna, G., Gregori, S., Magistrelli, G., Isacchi, A., Adorini, L. (2000). Early Th1 Response in Unprimed Nonobese Diabetic Mice to the Tyrosine Phosphatase-Like Insulinoma-Associated Protein 2, an Autoantigen in Type 1 Diabetes. J. Immunol. 165: 6748-6755 [Abstract] [Full Text]
HASKÓ, G., KUHEL, D. G., CHEN, J.-F., SCHWARZSCHILD, M. A., DEITCH, E. A., MABLEY, J. G., MARTON, A., SZABÓ, C. (2000). Adenosine inhibits IL-12 and TNF-{alpha} production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J. 14: 2065-2074 [Abstract] [Full Text]
Park, A. Y., Hondowicz, B. D., Scott, P. (2000). IL-12 Is Required to Maintain a Th1 Response During Leishmania major Infection. J. Immunol. 165: 896-902 [Abstract] [Full Text]
Karachunski, P. I., Ostlie, N. S., Monfardini, C., Conti-Fine, B. M. (2000). Absence of IFN-{gamma} or IL-12 Has Different Effects on Experimental Myasthenia Gravis in C57BL/6 Mice. J. Immunol. 164: 5236-5244 [Abstract] [Full Text]
Pagenstecher, A., Lassmann, S., Carson, M. J., Kincaid, C. L., Stalder, A. K., Campbell, I. L. (2000). Astrocyte-Targeted Expression of IL-12 Induces Active Cellular Immune Responses in the Central Nervous System and Modulates Experimental Allergic Encephalomyelitis. J. Immunol. 164: 4481-4492 [Abstract] [Full Text]
Joosten, L. A B, Helsen, M. M A, van den Berg, W. B (2000). Blockade of endogenous interleukin 12 results in suppression of murine streptococcal cell wall arthritis by enhancement of interleukin 10 and interleukin 1Ra. Ann Rheum Dis 59: 196-205 [Abstract] [Full Text]
Falcone, M., Yeung, B., Tucker, L., Rodriguez, E., Sarvetnick, N. (1999). 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. JEM 190: 963-972 [Abstract] [Full Text]
Chen, Y., Boros, D. L. (1999). Polarization of the Immune Response to the Single Immunodominant Epitope of p38, a Major Schistosoma mansoni Egg Antigen, Generates Th1- or Th2-Type Cytokines and Granulomas. Infect. Immun. 67: 4570-4577 [Abstract] [Full Text]
Trembleau, S., Penna, G., Gregori, S., Chapman, H. D., Serreze, D. V., Magram, J., Adorini, L. (1999). Pancreas-Infiltrating Th1 Cells and Diabetes Develop in IL-12-Deficient Nonobese Diabetic Mice. J. Immunol. 163: 2960-2968 [Abstract] [Full Text]
Rothe, H., Hausmann, A., Casteels, K., Okamura, H., Kurimoto, M., Burkart, V., Mathieu, C., Kolb, H. (1999). IL-18 Inhibits Diabetes Development in Nonobese Diabetic Mice by Counterregulation of Th1-Dependent Destructive Insulitis. J. Immunol. 163: 1230-1236 [Abstract] [Full Text]
Bonifacio, E., Scirpoli, M., Kredel, K., Fuchtenbusch, M., Ziegler, A.-G. (1999). Early Autoantibody Responses in Prediabetes Are IgG1 Dominated and Suggest Antigen-Specific Regulation. J. Immunol. 163: 525-532 [Abstract] [Full Text]
Cowdery, J. S., Boerth, N. J., Norian, L. A., Myung, P. S., Koretzky, G. A. (1999). Differential Regulation of the IL-12 p40 Promoter and of p40 Secretion by CpG DNA and Lipopolysaccharide. J. Immunol. 162: 6770-6775 [Abstract] [Full Text]
Okubo, T., Hagiwara, E., Ohno, S., Tsuji, T., Ihata, A., Ueda, A., Shirai, A., Aoki, I., Okuda, K., Miyazaki, J.-i., Ishigatsubo, Y. (1999). Administration of an IL-12-Encoding DNA Plasmid Prevents the Development of Chronic Graft-Versus-Host Disease (GVHD). J. Immunol. 162: 4013-4017 [Abstract] [Full Text]
Boros, D. L., Whitfield, J. R. (1999). Enhanced Th1 and Dampened Th2 Responses Synergize To Inhibit Acute Granulomatous and Fibrotic Responses in Murine Schistosomiasis Mansoni. Infect. Immun. 67: 1187-1193 [Abstract] [Full Text]
Bradley, L. M., Asensio, V. C., Schioetz, L.-K., Harbertson, J., Krahl, T., Patstone, G., Woolf, N., Campbell, I. L., Sarvetnick, N. (1999). Islet-Specific Th1, But Not Th2, Cells Secrete Multiple Chemokines and Promote Rapid Induction of Autoimmune Diabetes. J. Immunol. 162: 2511-2520 [Abstract] [Full Text]
Bussolati, B., Mariano, F., Biancone, L., Foa, R., David, S., Cambi, V., Camussi, G. (1999). Interleukin-12 Is Synthesized by Mesangial Cells and Stimulates Platelet-Activating Factor Synthesis, Cytoskeletal Reorganization, and Cell Shape Change. Am. J. Pathol. 154: 623-632 [Abstract] [Full Text]
Girgis, L., Davis, M. M., de St. Groth, B. F. (1999). The Avidity Spectrum of T Cell Receptor Interactions Accounts for T Cell Anergy in a Double Transgenic Model. JEM 189: 265-278 [Abstract] [Full Text]
Car, B. D., Eng, V. M., Lipman, J. M., Anderson, T. D. (1999). The Toxicology of Interleukin-12: A Review. Toxicol Pathol 27: 58-63 [Abstract]
Bright, J. J., Du, C., Coon, M., Sriram, S., Klaus, S. J. (1998). Prevention of Experimental Allergic Encephalomyelitis via Inhibition of IL-12 Signaling and IL-12-Mediated Th1 Differentiation: An Effect of the Novel Anti-Inflammatory Drug Lisofylline. J. Immunol. 161: 7015-7022 [Abstract] [Full Text]
Lehuen, A., Lantz, O., Beaudoin, L., Laloux, V., Carnaud, C., Bendelac, A., Bach, J.-F., Monteiro, R. C. (1998). Overexpression of Natural Killer T Cells Protects V{alpha}14-J{alpha}281 Transgenic Nonobese Diabetic Mice against Diabetes. JEM 188: 1831-1839 [Abstract] [Full Text]
Inoue, A., Koh, C.-S., Yamazaki, M., Yahikozawa, H., Ichikawa, M., Yagita, H., Kim, B. S. (1998). Suppressive Effect on Theiler's Murine Encephalomyelitis Virus-Induced Demyelinating Disease by the Administration of Anti-IL-12 Antibody. J. Immunol. 161: 5586-5593 [Abstract] [Full Text]
Alegre, M.-L., Shiels, H., Thompson, C. B., Gajewski, T. F. (1998). Expression and Function of CTLA-4 in Th1 and Th2 Cells. J. Immunol. 161: 3347-3356 [Abstract] [Full Text]
Bright, J. J., Sriram, S. (1998). TGF-{beta} Inhibits IL-12-Induced Activation of Jak-STAT Pathway in T Lymphocytes. J. Immunol. 161: 1772-1777 [Abstract] [Full Text]
Gattorno, M, Picco, P, Vignola, S, Stalla, F, Buoncompagni, A, Pistoia, V (1998). Serum interleukin 12�concentration in juvenile chronic arthritis. Ann Rheum Dis 57: 425-428 [Abstract] [Full Text]
Martino, G, Furlan, R, Galbiati, F, Poliani, P L, Bergami, A, Grimaldi, L M., Adorini, L, Comi, G (1998). A gene therapy approach to treat demyelinating diseases using nonreplicative herpetic vectors engineered to produce cytokines. Mult Scler 4: 222-227 [Abstract]
Hammond, K. J.L., Poulton, L. D., Palmisano, L. J., Silveira, P. A., Godfrey, D. I., Baxter, A. G. (1998). {alpha}/{beta}-T Cell Receptor (TCR)+CD4-CD8- (NKT) Thymocytes Prevent Insulin-dependent Diabetes Mellitus in Nonobese Diabetic (NOD)/Lt Mice by the Influence of Interleukin (IL)-4 and/or IL-10. JEM 187: 1047-1056 [Abstract] [Full Text]
Segal, B. M., Dwyer, B. K., Shevach, E. M. (1998). An Interleukin (IL)-10/IL-12 Immunoregulatory Circuit Controls Susceptibility to Autoimmune Disease. JEM 187: 537-546 [Abstract] [Full Text]
Bagenstose, L. M., Salgame, P., Monestier, M. (1998). IL-12 Down-Regulates Autoantibody Production in Mercury-Induced Autoimmunity. J. Immunol. 160: 1612-1617 [Abstract] [Full Text]
Sutterwala, F. S., Noel, G. J., Clynes, R., Mosser, D. M. (1997). Selective Suppression of Interleukin-12 Induction after Macrophage Receptor Ligation. JEM 185: 1977-1985 [Abstract] [Full Text]
Balashov, K.�E., Smith, D.�R., Khoury, S.�J., Hafler, D.�A., Weiner, H.�L. (1997). Increased interleukin 12�production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40�ligand. Proc. Natl. Acad. Sci. USA 94: 599-603 [Abstract] [Full Text]
Kurrer, M.�O., Pakala, S.�V., Hanson, H.�L., Katz, J.�D. (1997). beta cell apoptosis in T cell-mediated�autoimmune�diabetes. Proc. Natl. Acad. Sci. USA 94: 213-218 [Abstract] [Full Text]
Katz, J., Benoist, C, Mathis, D (1995). T helper cell subsets in insulin-dependent diabetes. Science 268: 1185-1188 [Abstract]
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]