Abstract
Increasing evidence suggests that in addition to T cell-dependent effector mechanisms, autoantibodies are also involved in the pathogenesis of MS, including demyelinating antibodies specific for myelin oligodendrocyte glycoprotein (MOG). Our previous studies have demonstrated that recombinant T cell receptor ligands (RTLs) are very effective for treating T cell-mediated experimental autoimmune encephalomyelitis (EAE). In order to expand the scope of RTL therapy in MS patients, it was of interest to study RTL treatment of EAE involving a demyelinating antibody component. Therefore, we evaluated the therapeutic effects of RTL551, specific for T cells reactive to mouse (m)MOG-35-55 peptide, on EAE induced with recombinant human (rh)MOG in C57BL/6 mice. We report that RTL551 therapy can reverse disease progression and reduce demyelination and axonal damage induced by rhMOG without suppressing the anti-MOG antibody response. This result suggests that T cell-mediated inflammation and associated blood–brain barrier dysfunction are the central contributors to EAE pathogenesis and that successful regulation of these key players restricts potential damage by demyelinating antibodies. The results of our study lend support for the use of RTL therapy for treatment of MS subjects whose disease includes inflammatory T cells as well as those with an additional antibody component.
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Acknowledgments
The authors wish to thank Ms. Eva K. Niehaus for assistance in manuscript preparation. Dr. Sinha is a Postdoctoral Fellow of the National Multiple Sclerosis Society, and this work was supported in part by National Multiple Sclerosis Society Postdoctoral Fellowship FG1749-A-1 and National Multiple Sclerosis Society grants RG3794-A-4, RG3468, and RG3844A2/1; Multiple Sclerosis Society grant 874/07; National Institutes of Health grants NS47661, AI43960, and NS46877; The Nancy Davis Center Without Walls; The Biomedical Laboratory R&D Service, Department of Veterans Affairs; The National Health and Medical Research Council of Australia, The Baker Foundation; and the Bellberry Ltd Fund.
Conflict of interest
Drs. Burrows, Offner, Vandenbark, and OHSU have a significant financial interest in Artielle ImmunoTherapeutics, Inc., a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by the OHSU and VAMC Conflict of Interest in Research Committees.
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Sinha, S., Subramanian, S., Emerson-Webber, A. et al. Recombinant TCR Ligand Reverses Clinical Signs and CNS Damage of EAE Induced by Recombinant Human MOG. J Neuroimmune Pharmacol 5, 231–239 (2010). https://doi.org/10.1007/s11481-009-9175-1
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DOI: https://doi.org/10.1007/s11481-009-9175-1