Recombinant TCR ligand reverses clinical signs and CNS damage of EAE induced by recombinant human MOG

Sushmita Sinha, Sandhya Subramanian, Ashley Emerson-Webber, Maren Lindner, Gregory G. Burrows, Marjorie Grafe, Christopher Linington, Arthur A. Vandenbark, Claude C.A. Bernard, Halina Offner

Research output: Contribution to journalArticle

14 Scopus citations

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 Tcell 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 bloodbrain 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.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalJournal of Neuroimmune Pharmacology
Volume5
Issue number2
DOIs
StatePublished - Jun 1 2010

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Keywords

  • CNS damage
  • EAE
  • MS
  • Recombinant human MOG

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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