The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Samoilova, E. B.
Right arrow Articles by Chen, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Samoilova, E. B.
Right arrow Articles by Chen, Y.
The Journal of Immunology, 1998, 161: 6480-6486.
Copyright © 1998 by The American Association of Immunologists

IL-6-Deficient Mice Are Resistant to Experimental Autoimmune Encephalomyelitis: Roles of IL-6 in the Activation and Differentiation of Autoreactive T Cells1

Elena B. Samoilova, Jennifer L. Horton, Brendan Hilliard, Tzu-Shang T. Liu and Youhai Chen2

Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Although autoreactive T cells recognizing self myelin Ags are present in most individuals, autoimmune disease of the central nervous system is a relatively rare medical condition. Development of autoimmune disease may require not only the presence of autoreactive T cells but also that autoreactive T cells become activated. Activation of T cells may require a minimum of two signals: an Ag-specific signal delivered by MHC-peptide complex and a second signal delivered by costimulatory molecules or cytokines. Although in vitro studies have suggested that cytokines, especially proinflammatory cytokines such as IL-1, IL-6, and TNF are involved in T cell activation, their precise roles in vivo are not clear. To determine the roles of proinflammatory cytokines in T cell activation in vivo and in the development of autoimmune disease, we have studied experimental autoimmune encephalomyelitis (EAE) in mice deficient in IL-6. We found that IL-6-deficient mice were completely resistant to EAE induced by myelin oligodendrocyte glycoprotein (MOG), whereas IL-6-competent control mice developed EAE characterized by focal inflammation and demyelination in the central nervous system and deficiency in neurologic functions. Furthermore, we established that the resistance to EAE in IL-6-deficient mice was associated with a deficiency of MOG-specific T cells to differentiate into either Th1 or Th2 type effector cells in vivo. These results strongly suggest that IL-6 plays a crucial role in the activation and differentiation of autoreactive T cells in vivo and that blocking IL-6 function can be an effective means to prevent EAE.




This article has been cited by other articles:


Home page
 JEMHome page
J. Das, G. Ren, L. Zhang, A. I. Roberts, X. Zhao, A. L.M. Bothwell, L. Van Kaer, Y. Shi, and G. Das
Transforming growth factor {beta} is dispensable for the molecular orchestration of Th17 cell differentiation
J. Exp. Med., October 26, 2009; 206(11): 2407 - 2416.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. T. Gurfein, Y. Zhang, C. B. Lopez, A. T. Argaw, A. Zameer, T. M. Moran, and G. R. John
IL-11 Regulates Autoimmune Demyelination
J. Immunol., October 1, 2009; 183(7): 4229 - 4240.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Quintana, M. Muller, R. F. Frausto, R. Ramos, D. R. Getts, E. Sanz, M. J. Hofer, M. Krauthausen, N. J. C. King, J. Hidalgo, et al.
Site-Specific Production of IL-6 in the Central Nervous System Retargets and Enhances the Inflammatory Response in Experimental Autoimmune Encephalomyelitis
J. Immunol., August 1, 2009; 183(3): 2079 - 2088.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
S. Siegemund, N. Schutze, S. Schulz, K. Wolk, K. Nasilowska, R. K. Straubinger, R. Sabat, and G. Alber
Differential IL-23 requirement for IL-22 and IL-17A production during innate immunity against Salmonella enterica serovar Enteritidis
Int. Immunol., May 1, 2009; 21(5): 555 - 565.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
H. Shen and D. R. Goldstein
IL-6 and TNF-{alpha} Synergistically Inhibit Allograft Acceptance
J. Am. Soc. Nephrol., May 1, 2009; 20(5): 1032 - 1040.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
I. Gonzalez-Garcia, Y. Zhao, S. Ju, Q. Gu, L. Liu, J. K. Kolls, and B. Lu
IL-17 Signaling-Independent Central Nervous System Autoimmunity Is Negatively Regulated by TGF-{beta}
J. Immunol., March 1, 2009; 182(5): 2665 - 2671.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Wang, D. Feng, G. Liu, Q. Luo, Y. Xu, S. Lin, J. Fei, and L. Xu
{gamma}-Aminobutyric Acid Transporter 1 Negatively Regulates T Cell-Mediated Immune Responses and Ameliorates Autoimmune Inflammation in the CNS
J. Immunol., December 15, 2008; 181(12): 8226 - 8236.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. M. Brenchley, M. Paiardini, K. S. Knox, A. I. Asher, B. Cervasi, T. E. Asher, P. Scheinberg, D. A. Price, C. A. Hage, L. M. Kholi, et al.
Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections
Blood, October 1, 2008; 112(7): 2826 - 2835.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
I. Sonderegger, G. Iezzi, R. Maier, N. Schmitz, M. Kurrer, and M. Kopf
GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival
J. Exp. Med., September 29, 2008; 205(10): 2281 - 2294.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Serada, M. Fujimoto, M. Mihara, N. Koike, Y. Ohsugi, S. Nomura, H. Yoshida, T. Nishikawa, F. Terabe, T. Ohkawara, et al.
IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis
PNAS, July 1, 2008; 105(26): 9041 - 9046.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Schulte, G. K. Sukhova, and P. Libby
Genetically Programmed Biases in Th1 and Th2 Immune Responses Modulate Atherogenesis
Am. J. Pathol., June 1, 2008; 172(6): 1500 - 1508.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Roy, X. Liu, and K. Pahan
Myelin Basic Protein-primed T Cells Induce Neurotrophins in Glial Cells via {alpha}5beta3 Integrin
J. Biol. Chem., November 2, 2007; 282(44): 32222 - 32232.
[Abstract] [Full Text] [PDF]

Home page
 Trauma Violence AbuseHome page
M. W. Meagher, R. R. Johnson, E. G. Vichaya, E. E. Young, S. Lunt, and C. J. Welsh
Social Conflict Exacerbates an Animal Model of Multiple Sclerosis
Trauma Violence Abuse, July 1, 2007; 8(3): 314 - 330.
[Abstract] [PDF]

Home page
 J. Immunol.Home page
J. M. Reynolds, Q. Liu, K. C. Brittingham, Y. Liu, M. Gruenthal, C. Z. Gorgun, G. S. Hotamisligil, R. D. Stout, and J. Suttles
Deficiency of Fatty Acid-Binding Proteins in Mice Confers Protection from Development of Experimental Autoimmune Encephalomyelitis
J. Immunol., July 1, 2007; 179(1): 313 - 321.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
X. Chen, O. M. Z. Howard, and J. J. Oppenheim
Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells
J. Immunol., May 15, 2007; 178(10): 6123 - 6129.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
I. Herrmann, M. Kellert, A. Spreer, J. Gerber, H. Eiffert, M. Prinz, and R. Nau
Minocycline delays but does not attenuate the course of experimental autoimmune encephalomyelitis in Streptococcus pneumoniae-infected mice
J. Antimicrob. Chemother., January 1, 2007; 59(1): 74 - 79.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
W. E. Walker, I. W. Nasr, G. Camirand, B. M. Tesar, C. J. Booth, and D. R. Goldstein
Absence of Innate MyD88 Signaling Promotes Inducible Allograft Acceptance
J. Immunol., October 15, 2006; 177(8): 5307 - 5316.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
I. Herrmann, M. Kellert, H. Schmidt, A. Mildner, U. K. Hanisch, W. Bruck, M. Prinz, and R. Nau
Streptococcus pneumoniae Infection Aggravates Experimental Autoimmune Encephalomyelitis via Toll-Like Receptor 2.
Infect. Immun., August 1, 2006; 74(8): 4841 - 4848.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
J. L. Stark and A. H. Cross
Differential expression of suppressors of cytokine signaling-1 and -3 and related cytokines in central nervous system during remitting versus non-remitting forms of experimental autoimmune encephalomyelitis
Int. Immunol., February 1, 2006; 18(2): 347 - 353.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. C. Jenmalm, H. Cherwinski, E. P. Bowman, J. H. Phillips, and J. D. Sedgwick
Regulation of Myeloid Cell Function through the CD200 Receptor
J. Immunol., January 1, 2006; 176(1): 191 - 199.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Sun, B. Hilliard, L. Xu, and Y. H. Chen
Essential Roles of the Fas-Associated Death Domain in Autoimmune Encephalomyelitis
J. Immunol., October 1, 2005; 175(7): 4783 - 4788.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Dasgupta, M. Jana, X. Liu, and K. Pahan
Myelin Basic Protein-primed T Cells of Female but Not Male Mice Induce Nitric-oxide Synthase and Proinflammatory Cytokines in Microglia: IMPLICATIONS FOR GENDER BIAS IN MULTIPLE SCLEROSIS
J. Biol. Chem., September 23, 2005; 280(38): 32609 - 32617.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
Y. Kihara, S. Ishii, Y. Kita, A. Toda, A. Shimada, and T. Shimizu
Dual phase regulation of experimental allergic encephalomyelitis by platelet-activating factor
J. Exp. Med., September 19, 2005; 202(6): 853 - 863.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Offner, S. Subramanian, C. Wang, M. Afentoulis, A. A. Vandenbark, J. Huan, and G. G. Burrows
Treatment of Passive Experimental Autoimmune Encephalomyelitis in SJL Mice with a Recombinant TCR Ligand Induces IL-13 and Prevents Axonal Injury
J. Immunol., September 15, 2005; 175(6): 4103 - 4111.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
I. Rochman, W. E. Paul, and S. Z. Ben-Sasson
IL-6 Increases Primed Cell Expansion and Survival
J. Immunol., April 15, 2005; 174(8): 4761 - 4767.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
K. Kitamura, Y. Nakamoto, S. Kaneko, and N. Mukaida
Pivotal roles of interleukin-6 in transmural inflammation in murine T cell transfer colitis
J. Leukoc. Biol., December 1, 2004; 76(6): 1111 - 1117.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. M. Teague, R. M. Tempero, S. Thomas, K. Murali-Krishna, and B. H. Nelson
Proliferation and Differentiation of CD8+ T Cells in the Absence of IL-2/15 Receptor {beta}-Chain Expression or STAT5 Activation
J. Immunol., September 1, 2004; 173(5): 3131 - 3139.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
G. B. Di Gregorio, L. Hensley, T. Lu, G. Ranganathan, and P. A. Kern
Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity
Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E182 - E187.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. I. Bleier, V. G. Pillarisetty, A. B. Shah, and R. P. DeMatteo
Increased and Long-Term Generation of Dendritic Cells with Reduced Function from IL-6-Deficient Bone Marrow
J. Immunol., June 15, 2004; 172(12): 7408 - 7416.
[Abstract] [Full Text] [PDF]

Home page
 LupusHome page
E Tackey, P E Lipsky, and G G Illei
Rationale for interleukin-6 blockade in systemic lupus erythematosus
Lupus, May 1, 2004; 13(5): 339 - 343.
[Abstract] [PDF]

Home page
 Am. J. Pathol.Home page
C. Teuscher, M. E. Poynter, H. Offner, A. Zamora, T. Watanabe, P. D. Fillmore, J. F. Zachary, and E. P. Blankenhorn
Attenuation of Th1 Effector Cell Responses and Susceptibility to Experimental Allergic Encephalomyelitis in Histamine H2 Receptor Knockout Mice Is Due to Dysregulation of Cytokine Production by Antigen-Presenting Cells
Am. J. Pathol., March 1, 2004; 164(3): 883 - 892.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Dasgupta, M. Jana, X. Liu, and K. Pahan
Role of Very-late Antigen-4 (VLA-4) in Myelin Basic Protein-primed T Cell Contact-induced Expression of Proinflammatory Cytokines in Microglial Cells
J. Biol. Chem., June 13, 2003; 278(25): 22424 - 22431.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Fujino, N. Funeshima, Y. Kitazawa, H. Kimura, H. Amemiya, S. Suzuki, and X.-K. Li
Amelioration of Experimental Autoimmune Encephalomyelitis in Lewis Rats by FTY720 Treatment
J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 70 - 77.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
B. Schuster, M. Kovaleva, Y. Sun, P. Regenhard, V. Matthews, J. Grotzinger, S. Rose-John, and K.-J. Kallen
Signaling of Human Ciliary Neurotrophic Factor (CNTF) Revisited. THE INTERLEUKIN-6 RECEPTOR CAN SERVE AS AN alpha -RECEPTOR FOR CNTF
J. Biol. Chem., March 7, 2003; 278(11): 9528 - 9535.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
C. Pasare and R. Medzhitov
Toll Pathway-Dependent Blockade of CD4+CD25+ T Cell-Mediated Suppression by Dendritic Cells
Science, February 14, 2003; 299(5609): 1033 - 1036.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Subramanian, A. Matejuk, A. Zamora, A. A. Vandenbark, and H. Offner
Oral Feeding with Ethinyl Estradiol Suppresses and Treats Experimental Autoimmune Encephalomyelitis in SJL Mice and Inhibits the Recruitment of Inflammatory Cells into the Central Nervous System
J. Immunol., February 1, 2003; 170(3): 1548 - 1555.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
U. Eriksson, M. O. Kurrer, N. Schmitz, S. C. Marsch, A. Fontana, H.-P. Eugster, and M. Kopf
Interleukin-6-Deficient Mice Resist Development of Autoimmune Myocarditis Associated With Impaired Upregulation of Complement C3
Circulation, January 21, 2003; 107(2): 320 - 325.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
T. Atsumi, K. Ishihara, D. Kamimura, H. Ikushima, T. Ohtani, S. Hirota, H. Kobayashi, S.-J. Park, Y. Saeki, Y. Kitamura, et al.
A Point Mutation of Tyr-759 in Interleukin 6 Family Cytokine Receptor Subunit gp130 Causes Autoimmune Arthritis
J. Exp. Med., October 7, 2002; 196(7): 979 - 990.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Deng, E. Goluszko, E. Tuzun, H. Yang, and P. Christadoss
Resistance to Experimental Autoimmune Myasthenia Gravis in IL-6-Deficient Mice Is Associated with Reduced Germinal Center Formation and C3 Production
J. Immunol., July 15, 2002; 169(2): 1077 - 1083.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
R. R. Fenton, S. Molesworth-Kenyon, J. E. Oakes, and R. N. Lausch
Linkage of IL-6 with Neutrophil Chemoattractant Expression in Virus-Induced Ocular Inflammation
Invest. Ophthalmol. Vis. Sci., March 1, 2002; 43(3): 737 - 743.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. C. Ndhlovu, N. Ishii, K. Murata, T. Sato, and K. Sugamura
Critical Involvement of OX40 Ligand Signals in the T Cell Priming Events During Experimental Autoimmune Encephalomyelitis
J. Immunol., September 1, 2001; 167(5): 2991 - 2999.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
R. G. Titus, G. K. DeKrey, R. V. Morris, and M. B. P. Soares
Interleukin-6 Deficiency Influences Cytokine Expression in Susceptible BALB Mice Infected with Leishmania major but Does Not Alter the Outcome of Disease
Infect. Immun., August 1, 2001; 69(8): 5189 - 5192.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
U. Grohmann, F. Fallarino, R. Bianchi, M. L. Belladonna, C. Vacca, C. Orabona, C. Uyttenhove, M. C. Fioretti, and P. Puccetti
IL-6 Inhibits the Tolerogenic Function of CD8{{alpha}}+ Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase
J. Immunol., July 15, 2001; 167(2): 708 - 714.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
S. A. Huber, P. Sakkinen, C. David, M. K. Newell, and R. P. Tracy
T Helper-Cell Phenotype Regulates Atherosclerosis in Mice Under Conditions of Mild Hypercholesterolemia
Circulation, May 29, 2001; 103(21): 2610 - 2616.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Yamamoto, K. Yoshizaki, T. Kishimoto, and H. Ito
IL-6 Is Required for the Development of Th1 Cell-Mediated Murine Colitis
J. Immunol., May 1, 2000; 164(9): 4878 - 4882.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Ohta, B. Wiggert, S. Yamagami, A. W. Taylor, and J. W. Streilein
Analysis of Immunomodulatory Activities of Aqueous Humor from Eyes of Mice with Experimental Autoimmune Uveitis
J. Immunol., February 1, 2000; 164(3): 1185 - 1192.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 J. Biol. Chem.Home page
T. V. Petrova, K. T. Akama, and L. J. Van Eldik
Selective Modulation of BV-2 Microglial Activation by Prostaglandin E2. DIFFERENTIAL EFFECTS ON ENDOTOXIN-STIMULATED CYTOKINE INDUCTION
J. Biol. Chem., October 1, 1999; 274(40): 28823 - 28827.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. Hilliard, E. B. Samoilova, T.-S. T. Liu, A. Rostami, and Y. Chen
Experimental Autoimmune Encephalomyelitis in NF-{kappa}B- Deficient Mice: Roles of NF-{kappa}B in the Activation and Differentiation of Autoreactive T Cells
J. Immunol., September 1, 1999; 163(5): 2937 - 2943.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1998 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1998 by The American Association of Immunologists, Inc. All rights reserved.