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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huan, J. Articles by Offner, H. Search for Related Content PubMed PubMed Citation Articles by Huan, J. Articles by Offner, H.

Monomeric Recombinant TCR Ligand Reduces Relapse Rate and Severity of Experimental Autoimmune Encephalomyelitis in SJL/J Mice through Cytokine Switch¹

Jianya Huan^2,*, Sandhya Subramanian^2,, Richard Jones^*, Cathleen Rich, Jason Link^*, Jeff Mooney^*, Dennis N. Bourdette^*, Arthur A. Vandenbark^*,,, Gregory G. Burrows^* and Halina Offner^3,*

Departments of ^* Neurology and Molecular Microbiology and Immunology, Oregon Health and Science University, and Veterans Affairs Medical Center, Portland, OR 97207

Our previous studies demonstrated that oligomeric recombinant TCR ligands (RTL) can treat clinical signs of experimental autoimmune encephalomyelitis (EAE) and induce long-term T cell tolerance against encephalitogenic peptides. In the current study, we produced a monomeric I-A^s/PLP 139-151 peptide construct (RTL401) suitable for use in SJL/J mice that develop relapsing disease after injection of PLP 139-151 peptide in CFA. RTL401 given i.v. or s.c. but not empty RTL400 or free PLP 139-151 peptide prevented relapses and significantly reduced clinical severity of EAE induced by PLP 139-151 peptide in SJL/J or (C57BL/6 x SJL)F₁ mice, but did not inhibit EAE induced by PLP 178-191 or MBP 84-104 peptides in SJL/J mice, or MOG 35-55 peptide in (C57BL/6 x SJL/J)F₁ mice. RTL treatment of EAE caused stable or enhanced T cell proliferation and secretion of IL-10 in the periphery, but reduced secretion of inflammatory cytokines and chemokines. In CNS, there was a modest reduction of inflammatory cells, reduced expression of very late activation Ag-4, lymphocyte function-associated Ag-1, and inflammatory cytokines, chemokines, and chemokine receptors, but enhanced expression of Th2-related factors, IL-10, TGF-3, and CCR3. These results suggest that monomeric RTL therapy induces a cytokine switch that curbs the encephalitogenic potential of PLP 139-151-specific T cells without fully preventing their entry into CNS, wherein they reduce the severity of inflammation. This mechanism differs from that observed using oligomeric RTL therapy in other EAE models. These results strongly support the clinical application of this novel class of peptide/MHC class II constructs in patients with multiple sclerosis who have focused T cell responses to known encephalitogenic myelin peptides.

This article has been cited by other articles:

				K. W. Wegmann, C. R. Wagner, R. H. Whitham, and D. J. Hinrichs Synthetic Peptide Dendrimers Block the Development and Expression of Experimental Allergic Encephalomyelitis J. Immunol., September 1, 2008; 181(5): 3301 - 3309. [Abstract] [Full Text] [PDF]

				J. Huan, L. J. Kaler, J. L. Mooney, S. Subramanian, C. Hopke, A. A. Vandenbark, E. F. Rosloniec, G. G. Burrows, and H. Offner MHC Class II Derived Recombinant T Cell Receptor Ligands Protect DBA/1LacJ Mice from Collagen-Induced Arthritis J. Immunol., January 15, 2008; 180(2): 1249 - 1257. [Abstract] [Full Text] [PDF]

				S. Sinha, S. Subramanian, T. M. Proctor, L. J. Kaler, M. Grafe, R. Dahan, J. Huan, A. A. Vandenbark, G. G. Burrows, and H. Offner A Promising Therapeutic Approach for Multiple Sclerosis: Recombinant T-Cell Receptor Ligands Modulate Experimental Autoimmune Encephalomyelitis by Reducing Interleukin-17 Production and Inhibiting Migration of Encephalitogenic Cells into the CNS J. Neurosci., November 14, 2007; 27(46): 12531 - 12539. [Abstract] [Full Text] [PDF]

				G. Adamus, G. G. Burrows, A. A. Vandenbark, and H. Offner Treatment of Autoimmune Anterior Uveitis with Recombinant TCR Ligands. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2555 - 2561. [Abstract] [Full Text] [PDF]

				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]

				M. J. Polanczyk, R. E. Jones, S. Subramanian, M. Afentoulis, C. Rich, M. Zakroczymski, P. Cooke, A. A. Vandenbark, and H. Offner T Lymphocytes Do Not Directly Mediate the Protective Effect of Estrogen on Experimental Autoimmune Encephalomyelitis Am. J. Pathol., December 1, 2004; 165(6): 2069 - 2077. [Abstract] [Full Text] [PDF]