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*
Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; and
Laboratory Service, Veterans Administration Health Care System, Palo Alto, CA 94304, and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305
Experimental autoimmune encephalomyelitis (EAE) and other
organ-specific autoimmune diseases are induced by autoantigen-specific
Th1 cells. In contrast, transfer of autoantigen-reactive Th2 cells that
produce IL-4 and IL-10 can prevent and/or reverse EAE. The relative
roles of these two Th2 cytokines in the regulation of EAE has not been
evaluated. Utilizing IL-4 and IL-10 knockout mice deficient for these
cytokines and IL-10 and IL-4 transgenic mice overexpressing these
cytokines, we demonstrate that IL-10-deficient mice
(IL-10-/-) are more susceptible and develop a more severe
EAE when compared with IL-4-deficient mice (IL-4-/-) or
wild-type mice. T cells from IL-10-/- mice exhibit a
stronger Ag-specific proliferation, produce more proinflammatory
cytokines (IFN-
and TNF-
) when stimulated with an
encephalitogenic peptide, and induce very severe EAE upon transfer into
wild-type mice. In contrast, while IL-4 transgenic mice develop similar
disease compared with their nontransgenic littermates, mice transgenic
for IL-10 are completely resistant to the development of EAE. Taken
together, our data suggest that IL-10 plays a more critical role
in the regulation of EAE by regulating autopathogenic Th1
responses.
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C. D. Pack, A. E. Cestra, B. Min, K. L. Legge, L. Li, J. C. Caprio-Young, J. J. Bell, R. K. Gregg, and H. Zaghouani Neonatal Exposure to Antigen Primes the Immune System to Develop Responses in Various Lymphoid Organs and Promotes Bystander Regulation of Diverse T Cell Specificities J. Immunol., October 15, 2001; 167(8): 4187 - 4195. [Abstract] [Full Text] [PDF]
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A. C. M. Johansson, A.-S. Hansson, K. S. Nandakumar, J. Backlund, and R. Holmdahl IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies J. Immunol., September 15, 2001; 167(6): 3505 - 3512. [Abstract] [Full Text] [PDF]
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S. M. Liva and R. R. Voskuhl Testosterone Acts Directly on CD4+ T Lymphocytes to Increase IL-10 Production J. Immunol., August 15, 2001; 167(4): 2060 - 2067. [Abstract] [Full Text] [PDF]
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A. Ito, B. F. Bebo Jr., A. Matejuk, A. Zamora, M. Silverman, A. Fyfe-Johnson, and H. Offner Estrogen Treatment Down-Regulates TNF-{{alpha}} Production and Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Cytokine Knockout Mice J. Immunol., July 1, 2001; 167(1): 542 - 552. [Abstract] [Full Text] [PDF]
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 R. R. Voskuhl and K. Palaszynski Sex Hormones in Experimental Autoimmune Encephalomyelitis: Implications for Multiple Sclerosis Neuroscientist, June 1, 2001; 7(3): 258 - 270. [Abstract] [PDF]
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A. J. Slavin, R. Maron, and H. L. Weiner Mucosal administration of IL-10 enhances oral tolerance in autoimmune encephalomyelitis and diabetes Int. Immunol., June 1, 2001; 13(6): 825 - 833. [Abstract] [Full Text] [PDF]
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N. S. Ostlie, P. I. Karachunski, W. Wang, C. Monfardini, M. Kronenberg, and B. M. Conti-Fine Transgenic Expression of IL-10 in T Cells Facilitates Development of Experimental Myasthenia Gravis J. Immunol., April 15, 2001; 166(8): 4853 - 4862. [Abstract] [Full Text] [PDF]
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A. E. Juedes and N. H. Ruddle Resident and Infiltrating Central Nervous System APCs Regulate the Emergence and Resolution of Experimental Autoimmune Encephalomyelitis J. Immunol., April 15, 2001; 166(8): 5168 - 5175. [Abstract] [Full Text] [PDF]
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O. S. Targoni, J. Baus, H. H. Hofstetter, M. D. Hesse, A. Y. Karulin, B. O. Boehm, T. G. Forsthuber, and P. V. Lehmann Frequencies of Neuroantigen-Specific T Cells in the Central Nervous System Versus the Immune Periphery During the Course of Experimental Allergic Encephalomyelitis J. Immunol., April 1, 2001; 166(7): 4757 - 4764. [Abstract] [Full Text] [PDF]
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D. Huang, J. Wang, P. Kivisakk, B. J. Rollins, and R. M. Ransohoff Absence of Monocyte Chemoattractant Protein 1 in Mice Leads to Decreased Local Macrophage Recruitment and Antigen-specific T Helper Cell Type 1 Immune Response in Experimental Autoimmune Encephalomyelitis J. Exp. Med., March 19, 2001; 193(6): 713 - 726. [Abstract] [Full Text] [PDF]
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D. J. Cua, B. Hutchins, D. M. LaFace, S. A. Stohlman, and R. L. Coffman Central Nervous System Expression of IL-10 Inhibits Autoimmune Encephalomyelitis J. Immunol., January 1, 2001; 166(1): 602 - 608. [Abstract] [Full Text] [PDF]
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A. Weishaupt, S. Jander, W. Bruck, T. Kuhlmann, M. Stienekemeier, T. Hartung, K. V. Toyka, G. Stoll, and R. Gold Molecular Mechanisms of High-Dose Antigen Therapy in Experimental Autoimmune Encephalomyelitis: Rapid Induction of Th1-Type Cytokines and Inducible Nitric Oxide Synthase J. Immunol., December 15, 2000; 165(12): 7157 - 7163. [Abstract] [Full Text] [PDF]
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A. G. Castro, M. Neighbors, S. D. Hurst, F. Zonin, R. A. Silva, E. Murphy, Y.-J. Liu, and A. O'Garra Anti-Interleukin 10 Receptor Monoclonal Antibody Is an Adjuvant for T Helper Cell Type 1 Responses to Soluble Antigen Only in the Presence of Lipopolysaccharide J. Exp. Med., November 20, 2000; 192(10): 1529 - 1534. [Abstract] [Full Text] [PDF]
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A. G.S. van Halteren, B. Mosselman, B. O. Roep, W. van Eden, A. Cooke, G. Kraal, and M. H. M. Wauben T Cell Reactivity to Heat Shock Protein 60 in Diabetes-Susceptible and Genetically Protected Nonobese Diabetic Mice Is Associated with a Protective Cytokine Profile J. Immunol., November 15, 2000; 165(10): 5544 - 5551. [Abstract] [Full Text] [PDF]
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H. Sasaki, L. Hou, A. Belani, C.-Y. Wang, T. Uchiyama, R. Muller, and P. Stashenko IL-10, But Not IL-4, Suppresses Infection-Stimulated Bone Resorption In Vivo J. Immunol., October 1, 2000; 165(7): 3626 - 3630. [Abstract] [Full Text] [PDF]
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E. M. Benkhart, M. Siedlar, A. Wedel, T. Werner, and H. W. L. Ziegler-Heitbrock Role of Stat3 in Lipopolysaccharide-Induced IL-10 Gene Expression J. Immunol., August 1, 2000; 165(3): 1612 - 1617. [Abstract] [Full Text] [PDF]
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S. C. Wilcoxen, E. Kirkman, K. C. Dowdell, and S. A. Stohlman Gender-Dependent IL-12 Secretion by APC Is Regulated by IL-10 J. Immunol., June 15, 2000; 164(12): 6237 - 6243. [Abstract] [Full Text] [PDF]
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E. Mizoguchi, A. Mizoguchi, F. I. Preffer, and A. K. Bhan Regulatory role of mature B cells in a murine model of inflammatory bowel disease Int. Immunol., May 1, 2000; 12(5): 597 - 605. [Abstract] [Full Text] [PDF]
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D. A. Young, L. D. Lowe, S. S. Booth, M. J. Whitters, L. Nicholson, V. K. Kuchroo, and M. Collins IL-4, IL-10, IL-13, and TGF-{beta} from an Altered Peptide Ligand-Specific Th2 Cell Clone Down-Regulate Adoptive Transfer of Experimental Autoimmune Encephalomyelitis J. Immunol., April 1, 2000; 164(7): 3563 - 3572. [Abstract] [Full Text] [PDF]
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E. H. Tran, E. N. Prince, and T. Owens IFN-{gamma} Shapes Immune Invasion of the Central Nervous System Via Regulation of Chemokines J. Immunol., March 1, 2000; 164(5): 2759 - 2768. [Abstract] [Full Text] [PDF]
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A. E. Juedes, P. Hjelmstrom, C. M. Bergman, A. L. Neild, and N. H. Ruddle Kinetics and Cellular Origin of Cytokines in the Central Nervous System: Insight into Mechanisms of Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis J. Immunol., January 1, 2000; 164(1): 419 - 426. [Abstract] [Full Text] [PDF]
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S. A. Stohlman, L. Pei, D. J. Cua, Z. Li, and D. R. Hinton Activation of Regulatory Cells Suppresses Experimental Allergic Encephalomyelitis Via Secretion of IL-10 J. Immunol., December 1, 1999; 163(11): 6338 - 6344. [Abstract] [Full Text] [PDF]
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S. Trembleau, G. Penna, S. Gregori, H. D. Chapman, D. V. Serreze, J. Magram, and L. Adorini Pancreas-Infiltrating Th1 Cells and Diabetes Develop in IL-12-Deficient Nonobese Diabetic Mice J. Immunol., September 1, 1999; 163(5): 2960 - 2968. [Abstract] [Full Text] [PDF]
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Y. Dong, W. M. Rohn, and E. N. Benveniste IFN-{gamma} Regulation of the Type IV Class II Transactivator Promoter in Astrocytes J. Immunol., April 15, 1999; 162(8): 4731 - 4739. [Abstract] [Full Text] [PDF]
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 S. Kim, S. M. Liva, M. A. Dalal, M. A. Verity, and R. R. Voskuhl Estriol ameliorates autoimmune demyelinating disease: Implications for multiple sclerosis Neurology, April 1, 1999; 52(6): 1230 - 1230. [Abstract] [Full Text] [PDF]
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H. L. Weiner Oral tolerance with Copolymer 1 for the treatment of multiple sclerosis PNAS, March 30, 1999; 96(7): 3333 - 3335. [Full Text] [PDF]
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D. J. Cua, H. Groux, D. R. Hinton, S. A. Stohlman, and R. L. Coffman Transgenic Interleukin 10 Prevents Induction of Experimental Autoimmune Encephalomyelitis J. Exp. Med., March 15, 1999; 189(6): 1005 - 1010. [Abstract] [Full Text] [PDF]
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W. Ma, W. Lim, K. Gee, S. Aucoin, D. Nandan, M. Kozlowski, F. Diaz-Mitoma, and A. Kumar The p38 Mitogen-activated Kinase Pathway Regulates the Human Interleukin-10 Promoter via the Activation of Sp1 Transcription Factor in Lipopolysaccharide-stimulated Human Macrophages J. Biol. Chem., April 20, 2001; 276(17): 13664 - 13674. [Abstract] [Full Text] [PDF]
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