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

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

    Research output: Contribution to journalArticleResearchpeer-review

    16 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)1 - 9
    Number of pages9
    JournalJournal of Neuroimmune Pharmacology
    VolumeE
    DOIs
    Publication statusPublished - 2010

    Cite this