title: MOG extracellular domain (p1-125) triggers elevated frequency of CXCR3+ CD4+ Th1 cells in the CNS of mice and induces greater incidence of severe EAE.
abstract: BACKGROUND
  Myelin-specific T cells are implicated in multiple sclerosis (MS) and drive experimental autoimmune encephalomyelitis (EAE). EAE is commonly induced with short peptides, whereas in MS, whole myelin proteins are available for immune response. We asked whether immunization with the immunoglobulin-like domain of myelin oligodendrocyte glycoprotein (MOG(Igd), residues 1-125) might induce distinct CD4+ T-cell response and/or a stronger CD8+ T-cell response, compared to the 21 amino acid immunodominant MHC II-associating peptide (p35-55).
  
  
  OBJECTIVE
  Compare both EAE and T-cell responses in C57BL/6 mice immunized with MOG(Igd) and MOG p35-55.
  
  
  METHODS
  Cytokine production, and chemokine receptor expression by CD4+ and CD8+ T cells in the mouse central nervous system (CNS), were analyzed by flow cytometry.
  
  
  RESULTS
  MOG(Igd) triggered progression to more severe EAE than MOG p35-55, despite similar time of onset and overall incidence. EAE in MOG(Igd)-immunized mice was characterized by an increased percentage of CXCR3+ interferon-γ-producing CD4+ T cells in CNS. The CD8+ T-cell response to both immunogens was similar.
  
  
  CONCLUSIONS
  Increased incidence of severe disease following MOG(Igd) immunization, accompanied by an increased percentage of CD4+ T cells in the CNS expressing CXCR3 and producing interferon-γ, identifies a pathogenic role for interferon-γ that is not seen when disease is induced with a single Major Histocompatibility Complex (MHC) II-associating epitope.
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Jyothi T
authors.initials: JT
authors.lastname: Mony
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Reza
authors.initials: R
authors.lastname: Khorooshi
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark towens@health.sdu.dk.
authors.forename: Trevor
authors.initials: T
authors.lastname: Owens
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D051381:Rats; D054367:Receptors, CXCR3 / Q000276:immunology* / Q000378:metabolism; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: C515188:Cxcr3 protein, mouse; D000939:Epitopes; C571328:Mog protein, rat; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D054367:Receptors, CXCR3; C000602291:myelin oligodendrocyte glycoprotein (1-125); C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma
keywords: Central nervous system; T cells; chemokine receptors; cytokines; experimental autoimmune encephalomyelitis; immunogen; inflammation; interferon gamma; mouse study; myelin oligodendrocyte glycoprotein