title: CD134 plays a crucial role in the pathogenesis of EAE and is upregulated in the CNS of patients with multiple sclerosis.
abstract: We investigated the role of the CD134 (also named OX40) molecule in experimental allergic encephalomyelitis (EAE) and multiple sclerosis (MS). We examined the susceptibility of Cd134(-/-) mice to EAE, an autoimmune murine model that is dependent on infiltrating CD4+ T lymphocytes reactive to myelin proteins. EAE induced by myelin oligodendrocyte glycoprotein (MOG) injection in Cd134(-/-) mice showed less severe clinical signs of disease and markedly reduced inflammatory infiltrates within the central nervous system (CNS). Resistance was associated with a strong reduction of pathogenic IFNgamma-producing T cells infiltrating the CNS of Cd134(-/-) mice. Furthermore, analysis of CNS tissue sections from EAE animals and MS patients revealed the presence of CD134+ cells that were localized in active lesions, mainly in perivascular infiltrates. The presence of CD134-expressing T cells in brain tissue of MS patients and EAE affected mice, together with the functional evidence provided by the significant decrease in disease score obtained in Cd134(-/-) mice, indicate that interfering with the CD134 molecule in T cells may be an appropriate target for therapeutic intervention in active MS.
authors.affiliation: Serono Pharmaceutical Research Institute, 14, Chemin Aulx, 1228 Plan-les Ouates, Switzerland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Carboni
authors.forename: Fahmy
authors.initials: F
authors.lastname: Aboul-Enein
authors.forename: Caroline
authors.initials: C
authors.lastname: Waltzinger
authors.forename: Nigel
authors.initials: N
authors.lastname: Killeen
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Peña-Rossi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D009186:Myelin Sheath / Q000473:pathology; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; D007371:Interferon-gamma