Journal ArticleDOI
Mechanisms of action of glatiramer acetate in multiple sclerosis.
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TLDR
Four major mechanisms of GA have been identified: competition with myelin-basic protein for binding to major histocompatibility complex (MHC) molecules, which presumably occur only in vitro and are therefore irrelevant for the in vivo effects of GA, while mechanisms 3 and 4 could occur in vivo and both could contribute to the clinical effects ofGA.Abstract:
Glatiramer acetate (GA, Copaxone [Teva Pharmaceuticals, Kansas City, MO], formerly known as copolymer-1) and interferon- (IFN)-β are both used for the immunomodulatory treatment of multiple sclerosis, but they act in different ways. Four major mechanisms of GA have been identified: 1) competition with myelin-basic protein (MBP) for binding to major histocompatibility complex (MHC) molecules; 2) competition of GA/MHC with MBP/MHC for binding to the T-cell receptor; 3) partial activation and tolerance induction of MBP-specific T cells (action as an altered peptide ligand); and 4) induction of GA-reactive T-helper 2- (TH2)-like regulatory cells. Of these four mechanisms, 1 and 2 presumably occur only in vitro and are therefore irrelevant for the in vivo effects of GA. In contrast, mechanisms 3 and 4 could occur in vivo and both could contribute to the clinical effects of GA.read more
Citations
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Journal ArticleDOI
Multiple Sclerosis: An Immune or Neurodegenerative Disorder?
Bruce D. Trapp,Klaus-Armin Nave +1 more
TL;DR: Data that support neurodegeneration as the major cause of irreversible neurological disability in MS patients are reviewed and it is questioned whether inflammatory demyelination is primary or secondary in the disease process.
Journal ArticleDOI
Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.
Douglas S. Goodin,Elliot M. Frohman,G. P. Garmany,J. Halper,William Likosky,Fred D. Lublin,D. H. Silberberg,W. H. Stuart,S. van den Noort +8 more
TL;DR: Clinical trials study patients for only short periods of time (2 or 3 years) and, therefore, use only short-term outcome measures to assess efficacy, and evaluation of the relative effectiveness of different therapies requires consideration of which outcome measure or measures are relevant to the goals of therapy.
Journal ArticleDOI
Type II monocytes modulate T cell-mediated central nervous system autoimmune disease
Martin S. Weber,Thomas Prod'homme,Sawsan Youssef,Shannon E. Dunn,Cynthia D Rundle,Linda Lee,Juan C. Patarroyo,Olaf Stüve,Raymond A. Sobel,Lawrence Steinman,Scott S. Zamvil +10 more
TL;DR: Adoptive transfer of type II monocytes reversed EAE, suppressed TH17 cell development and promoted both TH2 differentiation and expansion of Treg cells in recipient mice, identifying a central role for these cells in T cell immune modulation of autoimmunity.
Journal ArticleDOI
Inflammation and therapeutic vaccination in CNS diseases.
TL;DR: Evidence now suggests that syndromes such as Alzheimer's disease and stroke have important inflammatory and immune components and may be amenable to treatment by anti-inflammatory and immunotherapeutic approaches.
Journal ArticleDOI
Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3.
TL;DR: It was evident that in vitro treatment and administration with COP-I significantly raised the level of Foxp3 expression inCD4+ T cells and promoted conversion of CD4+CD25+ regulatory T cells in wild-type B6 mice but not in IFN-gamma knockout mice.
References
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Journal ArticleDOI
The expanding universe of T-cell subsets: Th1, Th2 and more
Tim R. Mosmann,Subash Sad +1 more
TL;DR: The increasing number of T-cell subsets defined by cytokine patterns; the differentiation pathways of CD4+ and CD8+ T cells; the contribution of other cell types to these patterns; and the cytokine interactions during infection and pregnancy are discussed.
Journal ArticleDOI
Copolymer 1 reduces relapse rate and improves disability in relapsing‐remitting multiple sclerosis Results of a phase III multicenter, double‐blind, placebo‐controlled trial
Kenneth P. Johnson,Benjamin Rix Brooks,Jeffrey A. Cohen,Corey C. Ford,Jonathan Goldstein,Robert P. Lisak,Lawrence W. Myers,H. S. Panitch,John W. Rose,R. B. Schiffer,Timothy Vollmer,L. P. Weiner,Jerry S. Wolinsky +12 more
TL;DR: It is demonstrated that copolymer 1 treatment can significantly and beneficially alter the course of relapsing-remitting multiple sclerosis in a well-tolerated fashion.
Journal ArticleDOI
Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein
TL;DR: In this paper, structural similarity between viral T cell epitopes and self-peptides could lead to the induction of an autoaggressive T cell response based on the structural requirements for both MHC class 11 binding and TCR recognition of an immunodominant myelin basic protein (MBP) peptide.
Journal ArticleDOI
Activated Human T Cells, B Cells, and Monocytes Produce Brain-derived Neurotrophic Factor In Vitro and in Inflammatory Brain Lesions: A Neuroprotective Role of Inflammation?
Martin Kerschensteiner,Eike Gallmeier,Lüder Behrens,Vivian Vargas Leal,Thomas Misgeld,Wolfgang E. F. Klinkert,Roland Kolbeck,Edmund Hoppe,Rosa-Laura Oropeza-Wekerle,Ilse Bartke,Christine Stadelmann,Hans Lassmann,Hartmut Wekerle,Reinhard Hohlfeld +13 more
TL;DR: Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable ininflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis, raising the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.
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