Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 56K) 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 Shaw, M. K. Articles by Fathman, C. G. Search for Related Content PubMed PubMed Citation Articles by Shaw, M. K. Articles by Fathman, C. G. Social Bookmarking                            What's this?

Brief Definitive Reports

Michael K. Shaw^*, James B. Lorens, Archana Dhawan^*, Richard DalCanto^*, Harley Y. Tse^¶, Alyssa B. Tran^*, Colleen Bonpane^*, Shanti L. Eswaran^*, Stefan Brocke, Nora Sarvetnick^**, Lawrence Steinman, Garry P. Nolan^,||, and C. Garrison Fathman^*

From the ^* Department of Medicine, Division of Immunology and Rheumatology, Department of Molecular Pharmacology, Department of Microbiology, and Department of Immunology, Department of Neurological Sciences, ^|| Department of Immunology, Stanford University School of Medicine, Stanford, California 94305-5111; ^¶ Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201; and ^** Department of Immunology, Scripps Research Institute, La Jolla, California 92034

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system which serves as a model for the human disease multiple sclerosis. We demonstrate here that encephalitogenic T cells, transduced with a retroviral gene, construct to express interleukin 4, and can delay the onset and reduce the severity of EAE when adoptively transferred to myelin basic protein–immunized mice. Thus, T lymphocytes transduced with retroviral vectors can deliver "regulatory cytokines" in a site-specific manner and may represent a viable therapeutic strategy for the treatment of autoimmune disease.

M.K. Shaw is the recipient of a fellowship from the National Multiple Sclerosis Society. J. B. Lorens is the recipient of a fellowship from the Norwegian Cancer Society. This work was supported by National Institutes of Health grants AI36535 and NO1-AR-6-2227.

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

This article has been cited by other articles:

• Maret, M., Ruffie, C., Periquet, B., Campo, A.-M., Menevret, M., Phelep, A., Dziewiszek, K., Druilhe, A., Pretolani, M. (2007). Liposomal Retinoic Acids Modulate Asthma Manifestations in Mice. J. Nutr. 137: 2730-2736 [Abstract] [Full Text]  
• Ponomarev, E. D., Maresz, K., Tan, Y., Dittel, B. N. (2007). CNS-Derived Interleukin-4 Is Essential for the Regulation of Autoimmune Inflammation and Induces a State of Alternative Activation in Microglial Cells. J. Neurosci. 27: 10714-10721 [Abstract] [Full Text]  
• Hill, N. J., Stotland, A. B., Sarvetnick, N. E. (2007). Distinct regulation of autoreactive CD4 T cell expansion by interleukin-4 under conditions of lymphopenia. J. Leukoc. Biol. 81: 757-765 [Abstract] [Full Text]  
• Kleinschek, M. A., Owyang, A. M., Joyce-Shaikh, B., Langrish, C. L., Chen, Y., Gorman, D. M., Blumenschein, W. M., McClanahan, T., Brombacher, F., Hurst, S. D., Kastelein, R. A., Cua, D. J. (2007). IL-25 regulates Th17 function in autoimmune inflammation. JEM 204: 161-170 [Abstract] [Full Text]  
• Fujio, K., Okamoto, A., Araki, Y., Shoda, H., Tahara, H., Tsuno, N. H., Takahashi, K., Kitamura, T., Yamamoto, K. (2006). Gene Therapy of Arthritis with TCR Isolated from the Inflamed Paw. J. Immunol. 177: 8140-8147 [Abstract] [Full Text]  
• Paintlia, A. S., Paintlia, M. K., Singh, I., Singh, A. K. (2006). IL-4-Induced Peroxisome Proliferator-Activated Receptor {gamma} Activation Inhibits NF-{kappa}B Trans Activation in Central Nervous System (CNS) Glial Cells and Protects Oligodendrocyte Progenitors under Neuroinflammatory Disease Conditions: Implication for CNS-Demyelinating Diseases. J. Immunol. 176: 4385-4398 [Abstract] [Full Text]  
• Jun, S., Gilmore, W., Callis, G., Rynda, A., Haddad, A., Pascual, D. W. (2005). A Live Diarrheal Vaccine Imprints a Th2 Cell Bias and Acts as an Anti-Inflammatory Vaccine. J. Immunol. 175: 6733-6740 [Abstract] [Full Text]  
• Skapenko, A., Kalden, J. R., Lipsky, P. E., Schulze-Koops, H. (2005). The IL-4 Receptor {alpha}-Chain-Binding Cytokines, IL-4 and IL-13, Induce Forkhead Box P3-Expressing CD25+CD4+ Regulatory T Cells from CD25-CD4+ Precursors. J. Immunol. 175: 6107-6116 [Abstract] [Full Text]  
• Schif-Zuck, S., Westermann, J., Netzer, N., Zohar, Y., Meiron, M., Wildbaum, G., Karin, N. (2005). Targeted Overexpression of IL-18 Binding Protein at the Central Nervous System Overrides Flexibility in Functional Polarization of Antigen-Specific Th2 Cells. J. Immunol. 174: 4307-4315 [Abstract] [Full Text]  
• Mekala, D. J., Alli, R. S., Geiger, T. L. (2005). IL-10-Dependent Suppression of Experimental Allergic Encephalomyelitis by Th2-Differentiated, Anti-TCR Redirected T Lymphocytes. J. Immunol. 174: 3789-3797 [Abstract] [Full Text]  
• Takacs, K., Du Roure, C., Nabarro, S., Dillon, N., McVey, J. H., Webster, Z., MacNeil, A., Bartok, I., Higgins, C., Gray, D., Merkenschlager, M., Fisher, A. G. (2004). The regulated long-term delivery of therapeutic proteins by using antigen-specific B lymphocytes. Proc. Natl. Acad. Sci. USA 101: 16298-16303 [Abstract] [Full Text]  
• Hohlfeld, R., Wekerle, H. (2004). Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines. Proc. Natl. Acad. Sci. USA 101: 14599-14606 [Abstract] [Full Text]  
• Anderson, A. C., Reddy, J., Nazareno, R., Sobel, R. A., Nicholson, L. B., Kuchroo, V. K. (2004). IL-10 Plays an Important Role in the Homeostatic Regulation of the Autoreactive Repertoire in Naive Mice. J. Immunol. 173: 828-834 [Abstract] [Full Text]  
• Skapenko, A., Niedobitek, G. U., Kalden, J. R., Lipsky, P. E., Schulze-Koops, H. (2004). Generation and Regulation of Human Th1-Biased Immune Responses In Vivo: A Critical Role for IL-4 and IL-10. J. Immunol. 172: 6427-6434 [Abstract] [Full Text]  
• La Flamme, A. C., Ruddenklau, K., Backstrom, B. T. (2003). Schistosomiasis Decreases Central Nervous System Inflammation and Alters the Progression of Experimental Autoimmune Encephalomyelitis. Infect. Immun. 71: 4996-5004 [Abstract] [Full Text]  
• Mora, A. L., Stephenson, L. M., Enerson, B., Youn, J., Keegan, A. D., Boothby, M. (2003). New Programming of IL-4 Receptor Signal Transduction in Activated T Cells: Stat6 Induction and Th2 Differentiation Mediated by IL-4R{alpha} Lacking Cytoplasmic Tyrosines. J. Immunol. 171: 1891-1900 [Abstract] [Full Text]  
• Annenkov, A. E., Daly, G. M., Brocker, T., Chernajovsky, Y. (2003). Clustering of immunoreceptor tyrosine-based activation motif-containing signalling subunits in CD4+ T cells is an optimal signal for IFN-{gamma} production, but not for the production of IL-4. Int Immunol 15: 665-677 [Abstract] [Full Text]  
• Cribbs, D. H., Ghochikyan, A., Vasilevko, V., Tran, M., Petrushina, I., Sadzikava, N., Babikyan, D., Kesslak, P., Kieber-Emmons, T., Cotman, C. W., Agadjanyan, M. G. (2003). Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with {beta}-amyloid. Int Immunol 15: 505-514 [Abstract] [Full Text]  
• Sewell, D., Qing, Z., Reinke, E., Elliot, D., Weinstock, J., Sandor, M., Fabry, Z. (2003). Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. Int Immunol 15: 59-69 [Abstract] [Full Text]  
• Hammer, M. H., Schroder, G., Risch, K., Flugel, A., Volk, H.-D., Lehmann, M., Ritter, T. (2002). Antigen-Dependent Transgene Expression in Kidney Transplantation: A Novel Approach Using Gene-Engineered T Lymphocytes. J. Am. Soc. Nephrol. 13: 511-518 [Abstract] [Full Text]  
• Liva, S. M., Voskuhl, R. R. (2001). Testosterone Acts Directly on CD4+ T Lymphocytes to Increase IL-10 Production. J. Immunol. 167: 2060-2067 [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]  
• Ito, A., Bebo, B. F. Jr., Matejuk, A., Zamora, A., Silverman, M., Fyfe-Johnson, A., Offner, H. (2001). Estrogen Treatment Down-Regulates TNF-{{alpha}} Production and Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Cytokine Knockout Mice. J. Immunol. 167: 542-552 [Abstract] [Full Text]  
• Afanasyeva, M., Wang, Y., Kaya, Z., Park, S., Zilliox, M. J., Schofield, B. H., Hill, S. L., Rose, N. R. (2001). Experimental Autoimmune Myocarditis in A/J mice Is an Interleukin-4-Dependent Disease with a Th2 Phenotype. Am. J. Pathol. 159: 193-203 [Abstract] [Full Text]  
• Yamamoto, A. M., Chernajovsky, Y., Lepault, F., Podhajcer, O., Feldmann, M., Bach, J.-F., Chatenoud, L. (2001). The Activity of Immunoregulatory T Cells Mediating Active Tolerance Is Potentiated in Nonobese Diabetic Mice by an IL-4-Based Retroviral Gene Therapy. J. Immunol. 166: 4973-4980 [Abstract] [Full Text]  
• Kluth, D. C., Ainslie, C. V., Pearce, W. P., Finlay, S., Clarke, D., Anegon, I., Rees, A. J. (2001). Macrophages Transfected with Adenovirus to Express IL-4 Reduce Inflammation in Experimental Glomerulonephritis. J. Immunol. 166: 4728-4736 [Abstract] [Full Text]  
• Huang, D., Wang, J., Kivisakk, P., Rollins, B. J., Ransohoff, R. M. (2001). 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. JEM 193: 713-726 [Abstract] [Full Text]  
• Croxford, J. L., Feldmann, M., Chernajovsky, Y., Baker, D. (2001). Different Therapeutic Outcomes in Experimental Allergic Encephalomyelitis Dependant Upon the Mode of Delivery of IL-10: A Comparison of the Effects of Protein, Adenoviral or Retroviral IL-10 Delivery into the Central Nervous System. J. Immunol. 166: 4124-4130 [Abstract] [Full Text]  
• Cua, D. J., Hutchins, B., LaFace, D. M., Stohlman, S. A., Coffman, R. L. (2001). Central Nervous System Expression of IL-10 Inhibits Autoimmune Encephalomyelitis. J. Immunol. 166: 602-608 [Abstract] [Full Text]  
• Lee, J., Mira-Arbibe, L., Ulevitch, R. J. (2000). TAK1 regulates multiple protein kinase cascades activated by bacterial lipopolysaccharide. J. Leukoc. Biol. 68: 909-915 [Abstract] [Full Text]  
• Tapping, R. I., Akashi, S., Miyake, K., Godowski, P. J., Tobias, P. S. (2000). Toll-Like Receptor 4, But Not Toll-Like Receptor 2, Is a Signaling Receptor for Escherichia and Salmonella Lipopolysaccharides. J. Immunol. 165: 5780-5787 [Abstract] [Full Text]  
• Legge, K. L., Min, B., Bell, J. J., Caprio, J. C., Li, L., Gregg, R. K., Zaghouani, H. (2000). Coupling of Peripheral Tolerance to Endogenous Interleukin 10 Promotes Effective Modulation of Myelin-Activated T Cells and Ameliorates Experimental Allergic Encephalomyelitis. JEM 191: 2039-2052 [Abstract] [Full Text]  
• Wilcoxen, S. C., Kirkman, E., Dowdell, K. C., Stohlman, S. A. (2000). Gender-Dependent IL-12 Secretion by APC Is Regulated by IL-10. J. Immunol. 164: 6237-6243 [Abstract] [Full Text]  
• Young, D. A., Lowe, L. D., Booth, S. S., Whitters, M. J., Nicholson, L., Kuchroo, V. K., Collins, M. (2000). 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. 164: 3563-3572 [Abstract] [Full Text]  
• Costa, G. L., Benson, J. M., Seroogy, C. M., Achacoso, P., Fathman, C. G., Nolan, G. P. (2000). Targeting Rare Populations of Murine Antigen-Specific T Lymphocytes by Retroviral Transduction for Potential Application in Gene Therapy for Autoimmune Disease. J. Immunol. 164: 3581-3590 [Abstract] [Full Text]  
• Croxford, J. L., Triantaphyllopoulos, K. A., Neve, R. M., Feldmann, M., Chernajovsky, Y., Baker, D. (2000). Gene Therapy for Chronic Relapsing Experimental Allergic Encephalomyelitis Using Cells Expressing a Novel Soluble p75 Dimeric TNF Receptor. J. Immunol. 164: 2776-2781 [Abstract] [Full Text]  
• Stohlman, S. A., Pei, L., Cua, D. J., Li, Z., Hinton, D. R. (1999). Activation of Regulatory Cells Suppresses Experimental Allergic Encephalomyelitis Via Secretion of IL-10. J. Immunol. 163: 6338-6344 [Abstract] [Full Text]  
• Ehrhardt, G. R.A., Leslie, K. B., Lee, F., Wieler, J. S., Schrader, J. W. (1999). M-Ras, a Widely Expressed 29-kD Homologue of p21 Ras: Expression of a Constitutively Active Mutant Results in Factor-Independent Growth of an Interleukin-3-Dependent Cell Line. Blood 94: 2433-2444 [Abstract] [Full Text]  
• Cua, D. J., Groux, H., Hinton, D. R., Stohlman, S. A., Coffman, R. L. (1999). Transgenic Interleukin 10 Prevents Induction of Experimental Autoimmune Encephalomyelitis. JEM 189: 1005-1010 [Abstract] [Full Text]  
• Suttles, J., Milhorn, D. M., Miller, R. W., Poe, J. C., Wahl, L. M., Stout, R. D. (1999). CD40 Signaling of Monocyte Inflammatory Cytokine Synthesis through an ERK1/2-dependent Pathway. A TARGET OF INTERLEUKIN ()-4 AND IL-10 ANTI-INFLAMMATORY ACTION. J. Biol. Chem. 274: 5835-5842 [Abstract] [Full Text]  
• 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]  
• Guy, J., Qi, X., Hauswirth, W. W. (1998). Adeno-associated viral-mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis. Proc. Natl. Acad. Sci. USA 95: 13847-13852 [Abstract] [Full Text]  
• Begolka, W. S., Vanderlugt, C. L., Rahbe, S. M., Miller, S. D. (1998). Differential Expression of Inflammatory Cytokines Parallels Progression of Central Nervous System Pathology in Two Clinically Distinct Models of Multiple Sclerosis. J. Immunol. 161: 4437-4446 [Abstract] [Full Text]  
• Chen, L. Z., Hochwald, G. M., Huang, C., Dakin, G., Tao, H., Cheng, C., Simmons, W. J., Dranoff, G., Thorbecke, G. J. (1998). Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta 1. Proc. Natl. Acad. Sci. USA 95: 12516-12521 [Abstract] [Full Text]  
• Bettelli, E., Prabhu Das, M., Howard, E. D., Weiner, H. L., Sobel, R. A., Kuchroo, V. K. (1998). IL-10 Is Critical in the Regulation of Autoimmune Encephalomyelitis as Demonstrated by Studies of IL-10- and IL-4-Deficient and Transgenic Mice. J. Immunol. 161: 3299-3306 [Abstract] [Full Text]  
• Stinissen, P., Medaer, R., Raus, J. (1998). Myelin reactive T cells in the autoimmune pathogenesis of multiple sclerosis. Mult Scler 4: 203-211 [Abstract]  
• 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]  
• Falcone, M., Rajan, A. J., Bloom, B. R., Brosnan, C. F. (1998). A Critical Role for IL-4 in Regulating Disease Severity in Experimental Allergic Encephalomyelitis as Demonstrated in IL-4-Deficient C57BL/6 Mice and BALB/c Mice. J. Immunol. 160: 4822-4830 [Abstract] [Full Text]  
• Croxford, J. L., Triantaphyllopoulos, K., Podhajcer, O. L., Feldmann, M., Baker, D., Chernajovsky, Y. (1998). Cytokine Gene Therapy in Experimental Allergic Encephalomyelitis by Injection of Plasmid DNA-Cationic Liposome Complex into the Central Nervous System. J. Immunol. 160: 5181-5187 [Abstract] [Full Text]  
• EVANS, C H, WHALEN, J D, EVANS, C H, GHIVIZZANI, S C, ROBBINS, P D (1998). Gene therapy in autoimmune diseases. Ann Rheum Dis 57: 125-127 [Full Text]  
• Zeng, D., Dick, M., Cheng, L., Amano, M., Dejbakhsh-Jones, S., Huie, P., Sibley, R., Strober, S. (1998). Subsets of Transgenic T Cells That Recognize CD1 Induce or Prevent Murine Lupus: Role of Cytokines. JEM 187: 525-536 [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]  
• Force, W. R., Cheung, T. C., Ware, C. F. (1997). Dominant Negative Mutants of TRAF3 Reveal an Important Role for the Coiled Coil Domains in Cell Death Signaling by the Lymphotoxin-beta Receptor. J. Biol. Chem. 272: 30835-30840 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS