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Diminished myelin-specific T cell activation associated with increase in CTLA4 and Fas molecules in multiple sclerosis patients treated with IFN-beta.
Authors:Dannie E M Hallal-Longo  Sandra R Mirandola  Elaine C Oliveira  Alessandro S Farias  Fernanda G Pereira  Irene L Metze  Carlos Otavio Brand?o  Heloísa H Ruocco  Benito P Damasceno  Leonilda M B Santos
Affiliation:Neuroimmunology Unit, Department of Microbiology and Immunology, Biology Institute, University of Campinas, UNICAMP, Campinas SP, Brazil.
Abstract:Multiple sclerosis (MS) is a chronic inflammatory disease of the white matter of the central nervous system (CNS) characterized by focal areas of demyelination. Interferon-beta (IFN-beta) provides an effective treatment that lessens the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (RRMS), but the mechanisms by which IFN-beta is efficient remain uncertain. The data presented here demonstrate that IFN-beta impairs the proliferative response to myelin basic protein (MBP) and myelin, as well as increasing the expression of the CTLA4 intracellular molecule. Moreover, this treatment increases the expression of surface Fas molecules and of the soluble form of these molecules. Our hypothesis is that the increase in Fas and CTLA4 molecules in MS patients may lead to lymphocyte apoptosis, which suggests possible mechanisms underlying the therapeutic response to IFN-beta.
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