HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ruiz, P. J. Articles by Steinman, L. Search for Related Content PubMed PubMed Citation Articles by Ruiz, P. J. Articles by Steinman, L.

Suppressive Immunization with DNA Encoding a Self-Peptide Prevents Autoimmune Disease: Modulation of T Cell Costimulation¹

Pedro J. Ruiz^*, Hideki Garren^*, Irene U. Ruiz, David L. Hirschberg^*, Louis-Vu T. Nguyen^*, Marcela V. Karpuj, Minton T. Cooper^*, Dennis J. Mitchell^*, C. Garrison Fathman and Lawrence Steinman^2,*,

Departments of ^* Neurology and Neurological Sciences and Medicine, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305; and Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

Usually we rely on vaccination to promote an immune response to a pathogenic microbe. In this study, we demonstrate a suppressive form of vaccination, with DNA encoding a minigene for residues 139–151 of myelin proteolipid protein (PLP_139–151), a pathogenic self-Ag. This suppressive vaccination attenuates a prototypic autoimmune disease, experimental autoimmune encephalomyelitis, which presents clinically with paralysis. Proliferative responses and production of the Th1 cytokines, IL-2 and IFN-, were reduced in T cells responsive to PLP_139–151. In the brains of mice that were successfully vaccinated, mRNA for IL-2, IL-15, and IFN- were reduced. A mechanism underlying the reduction in severity and incidence of paralytic autoimmune disease and the reduction in Th1 cytokines involves altered costimulation of T cells; loading of APCs with DNA encoding PLP_139–151 reduced the capacity of a T cell line reactive to PLP_139–151 to proliferate even in the presence of exogenous CD28 costimulation. DNA immunization with the myelin minigene for PLP-altered expression of B7.1 (CD80), and B7.2 (CD86) on APCs in the spleen. Suppressive immunization against self-Ags encoded by DNA may be exploited to treat autoimmune diseases.

This article has been cited by other articles:

				P. B. Silver, R. K. Agarwal, S.-B. Su, I. Suffia, R. S. Grajewski, D. Luger, C.-C. Chan, R. M. Mahdi, J. M. Nickerson, and R. R. Caspi Hydrodynamic Vaccination with DNA Encoding an Immunologically Privileged Retinal Antigen Protects from Autoimmunity through Induction of Regulatory T Cells J. Immunol., October 15, 2007; 179(8): 5146 - 5158. [Abstract] [Full Text] [PDF]

				A. Bar-Or, T. Vollmer, J. Antel, D. L. Arnold, C. A. Bodner, D. Campagnolo, J. Gianettoni, F. Jalili, N. Kachuck, Y. Lapierre, et al. Induction of Antigen-Specific Tolerance in Multiple Sclerosis After Immunization With DNA Encoding Myelin Basic Protein in a Randomized, Placebo-Controlled Phase 1/2 Trial Arch Neurol, October 1, 2007; 64(10): 1407 - 1415. [Abstract] [Full Text] [PDF]

				P. P. Ho, P. Fontoura, M. Platten, R. A. Sobel, J. J. DeVoss, L. Y. Lee, B. A. Kidd, B. H. Tomooka, J. Capers, A. Agrawal, et al. A Suppressive Oligodeoxynucleotide Enhances the Efficacy of Myelin Cocktail/IL-4-Tolerizing DNA Vaccination and Treats Autoimmune Disease J. Immunol., November 1, 2005; 175(9): 6226 - 6234. [Abstract] [Full Text] [PDF]

				R. Hohlfeld and H. Wekerle Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines PNAS, October 5, 2004; 101(suppl_2): 14599 - 14606. [Abstract] [Full Text] [PDF]

				P. P. Ho, P. Fontoura, P. J. Ruiz, L. Steinman, and H. Garren An Immunomodulatory GpG Oligonucleotide for the Treatment of Autoimmunity via the Innate and Adaptive Immune Systems J. Immunol., November 1, 2003; 171(9): 4920 - 4926. [Abstract] [Full Text] [PDF]

				C. Seifarth, S. Pop, B. Liu, C. P. Wong, and R. Tisch More Stringent Conditions of Plasmid DNA Vaccination Are Required to Protect Grafted Versus Endogenous Islets in Nonobese Diabetic Mice J. Immunol., July 1, 2003; 171(1): 469 - 476. [Abstract] [Full Text] [PDF]

				A. Lobell, R. Weissert, S. Eltayeb, K. L. de Graaf, J. Wefer, M. K. Storch, H. Lassmann, H. Wigzell, and T. Olsson Suppressive DNA Vaccination in Myelin Oligodendrocyte Glycoprotein Peptide-Induced Experimental Autoimmune Encephalomyelitis Involves a T1-Biased Immune Response J. Immunol., February 15, 2003; 170(4): 1806 - 1813. [Abstract] [Full Text] [PDF]

				I. Salomon, N. Netzer, G. Wildbaum, S. Schif-Zuck, G. Maor, and N. Karin Targeting the Function of IFN-{gamma}-Inducible Protein 10 Suppresses Ongoing Adjuvant Arthritis J. Immunol., September 1, 2002; 169(5): 2685 - 2693. [Abstract] [Full Text] [PDF]

				G. Wildbaum, N. Netzer, and N. Karin Plasmid DNA Encoding IFN-{gamma}-Inducible Protein 10 Redirects Antigen-Specific T Cell Polarization and Suppresses Experimental Autoimmune Encephalomyelitis J. Immunol., June 1, 2002; 168(11): 5885 - 5892. [Abstract] [Full Text] [PDF]

				D. Chabas, S. E. Baranzini, D. Mitchell, C. C. A. Bernard, S. R. Rittling, D. T. Denhardt, R. A. Sobel, C. Lock, M. Karpuj, R. Pedotti, et al. The Influence of the Proinflammatory Cytokine, Osteopontin, on Autoimmune Demyelinating Disease Science, November 23, 2001; 294(5547): 1731 - 1735. [Abstract] [Full Text] [PDF]

				A. Bot, D. Smith, S. Bot, A. Hughes, T. Wolfe, L. Wang, C. Woods, and M. v. Herrath Plasmid Vaccination with Insulin B Chain Prevents Autoimmune Diabetes in Nonobese Diabetic Mice J. Immunol., September 1, 2001; 167(5): 2950 - 2955. [Abstract] [Full Text] [PDF]

				D. J. Weaver Jr., B. Liu, and R. Tisch Plasmid DNAs Encoding Insulin and Glutamic Acid Decarboxylase 65 Have Distinct Effects on the Progression of Autoimmune Diabetes in Nonobese Diabetic Mice J. Immunol., July 1, 2001; 167(1): 586 - 592. [Abstract] [Full Text] [PDF]

				R. Tisch, B. Wang, D. J. Weaver, B. Liu, T. Bui, J. Arthos, and D. V. Serreze Antigen-Specific Mediated Suppression of {{beta}} Cell Autoimmunity by Plasmid DNA Vaccination J. Immunol., February 1, 2001; 166(3): 2122 - 2132. [Abstract] [Full Text] [PDF]

				G. Wildbaum, S. Youssef, and N. Karin A Targeted DNA Vaccine Augments the Natural Immune Response to Self TNF-{alpha} and Suppresses Ongoing Adjuvant Arthritis J. Immunol., November 15, 2000; 165(10): 5860 - 5866. [Abstract] [Full Text] [PDF]

				A. Lobell, R. Weissert, S. Eltayeb, C. Svanholm, T. Olsson, and H. Wigzell Presence of CpG DNA and the Local Cytokine Milieu Determine the Efficacy of Suppressive DNA Vaccination in Experimental Autoimmune Encephalomyelitis J. Immunol., November 1, 1999; 163(9): 4754 - 4762. [Abstract] [Full Text] [PDF]

				P. J. Ruiz, H. Garren, D. L. Hirschberg, A. M. Langer-Gould, M. Levite, M. V. Karpuj, S. Southwood, A. Sette, P. Conlon, and L. Steinman Microbial Epitopes Act as Altered Peptide Ligands to Prevent Experimental Autoimmune Encephalomyelitis J. Exp. Med., April 19, 1999; 189(8): 1275 - 1284. [Abstract] [Full Text] [PDF]

				R. Weissert, A. Lobell, K. L. de Graaf, S. Y. Eltayeb, R. Andersson, T. Olsson, and H. Wigzell Protective DNA vaccination against organ-specific autoimmunity is highly specific and discriminates between single amino acid substitutions in the peptide autoantigen PNAS, February 15, 2000; 97(4): 1689 - 1694. [Abstract] [Full Text] [PDF]