Recombinant TCR Ligand Reverses Clinical Signs and CNS Damage of EAE Induced by Recombinant Human MOG

Sinha, S., Subramanian, S., Emerson-Webber, A., Lindner, M., Burrows, G. G., Grafe, M., Linington, C. , Vandenbark, A. A., Bernard, C. C. A. and Offner, H. (2010) Recombinant TCR Ligand Reverses Clinical Signs and CNS Damage of EAE Induced by Recombinant Human MOG. Journal of Neuroimmune Pharmacology, 5(2), pp. 231-239. (doi: 10.1007/s11481-009-9175-1)

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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

Item Type:Articles
Keywords:ANTIBODIES Autoantibodies BARRIER BLOOD-BRAIN-BARRIER CELLS CNS CNS damage CYTOKINE SWITCH DISEASE DISEASE PROGRESSION DYSFUNCTION EAE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS GLYCOPROTEIN Human inflammation LIGAND MECHANISM MECHANISMS MICE MOUSE MS MULTIPLE-SCLEROSIS myelin MYELIN OLIGODENDROCYTE GLYCOPROTEIN pathogenesis PATIENT patients PATTERN PEPTIDE pharmacology PROGRESSION PROTEIN RAT RECEPTOR RECOMBINANT recombinant human MOG T cells T-cell T-CELLS THERAPY Treatment
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lindner, Dr Maren and Linington, Professor Christopher
Authors: Sinha, S., Subramanian, S., Emerson-Webber, A., Lindner, M., Burrows, G. G., Grafe, M., Linington, C., Vandenbark, A. A., Bernard, C. C. A., and Offner, H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Neuroimmune Pharmacology
ISSN:1557-1890

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