| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,¶
* Neuroimmunology Research and Tykeson Multiple Sclerosis Research Laboratory, Veterans Affairs Medical Center and Oregon Health & Science University, Portland, OR 97239; Departments of
Neurology and
Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239;
Department of Clinical Immunology, Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark; and
¶
Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, U.K.
In a previous study, we demonstrated that myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide could induce severe chronic experimental autoimmune encephalomyelitis (EAE) in HLA-DR2+ transgenic mice lacking all mouse MHC class II genes. We used this model to evaluate clinical efficacy and mechanism of action of a novel recombinant TCR ligand (RTL) comprised of the 
1 and 
1 domains of DR2 (DRB1*1501) covalently linked to the encephalitogenic MOG-35-55 peptide (VG312). We found that the MOG/DR2 VG312 RTL could induce long-term tolerance to MOG-35-55 peptide and reverse clinical and histological signs of EAE in a dose- and peptide-dependent manner. Some mice treated with lower doses of VG312 relapsed after cessation of daily treatment, but the mice could be successfully re-treated with a higher dose of VG312. Treatment with VG312 strongly reduced secretion of Th1 cytokines (TNF- and IFN-
) produced in response to MOG-35-55 peptide, and to a lesser degree purified protein derivative and Con A, but had no inhibitory effect on serum Ab levels to MOG-35-55 peptide. Abs specific for both the peptide and MHC moieties of the RTLs were also present after treatment with EAE, but these Abs had only a minor enhancing effect on T cell activation in vitro. These data demonstrate the powerful tolerance-inducing therapeutic effects of VG312 on MOG peptide-induced EAE in transgenic DR2 mice and support the potential of this approach to inhibit myelin Ag-specific responses in multiple sclerosis patients.
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]
|
|
|
|
|
|
A. P. Fontenot, T. S. Keizer, M. McCleskey, D. G. Mack, R. Meza-Romero, J. Huan, D. M. Edwards, Y. K. Chou, A. A. Vandenbark, B. Scott, et al. Recombinant HLA-DP2 Binds Beryllium and Tolerizes Beryllium-Specific Pathogenic CD4+ T Cells J. Immunol., September 15, 2006; 177(6): 3874 - 3883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Dzhambazov, K. S. Nandakumar, J. Kihlberg, L. Fugger, R. Holmdahl, and M. Vestberg Therapeutic Vaccination of Active Arthritis with a Glycosylated Collagen Type II Peptide in Complex with MHC Class II Molecules J. Immunol., February 1, 2006; 176(3): 1525 - 1533. [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]
|
|
|
|
 |
|
 E. N. Klyushnenkova, J. Link, W. T. Oberle, J. Kodak, C. Rich, A. A. Vandenbark, and R. B. Alexander Identification of HLA-DRB1*1501-Restricted T-cell Epitopes from Prostate-Specific Antigen Clin. Cancer Res., April 15, 2005; 11(8): 2853 - 2861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huan, S. Subramanian, R. Jones, C. Rich, J. Link, J. Mooney, D. N. Bourdette, A. A. Vandenbark, G. G. Burrows, and H. Offner Monomeric Recombinant TCR Ligand Reduces Relapse Rate and Severity of Experimental Autoimmune Encephalomyelitis in SJL/J Mice through Cytokine Switch J. Immunol., April 1, 2004; 172(7): 4556 - 4566. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
