title: T cell-activation in neuromyelitis optica lesions plays a role in their formation.
abstract: BACKGROUND
  Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS), which is characterized by the presence of pathogenic serum autoantibodies against aquaporin 4 (AQP4) in the vast majority of patients. The contribution of T cells to the formation of astrocyte destructive lesions is currently unclear. However, active human NMO lesions contain CD4+ T-lymphocytes expressing the activation marker Ox40, and the expression is more profound compared to that seen in MS lesions of comparable activity. Therefore, we analyzed the role of T-cell activation within the CNS in the initiation of NMO lesions in an experimental model of co-transfer of different encephalitogenic T-cells and human AQP4 antibody containing NMO immunoglobulin (NMO IgG). We further studied the expression of the T-cell activation marker Ox40 in NMO and multiple sclerosis lesions in different stages of activity.
  
  
  RESULTS
  All encephalitogenic T-cell lines used in our experiments induced brain inflammation with a comparable extent of blood brain barrier damage, allowing human NMO IgG to penetrate into the brain and spinal cord tissue. However, astrocyte destructive NMO lesions were only seen with T-cells, which showed signs of activation in the lesions. T-cell activation was reflected by the expression of the activation marker Ox40 and pronounced production of γ-IFN, which was able to increase the production of complement proteins and of the Fc gamma III receptor (Fcgr3) and decreased production of complement inhibitory protein Factor H in microglia.
  
  
  CONCLUSIONS
  Our data indicate that local activation of T-cells provide an inflammatory environment in the CNS, which allows AQP4 auto-antibodies to induce astrocyte destructive NMO-like lesions.
authors.forename: Maria
authors.initials: M
authors.lastname: Pohl
authors.forename: Naoto
authors.initials: N
authors.lastname: Kawakami
authors.forename: Maja
authors.initials: M
authors.lastname: Kitic
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Rui
authors.initials: R
authors.lastname: Martins
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Fischer
authors.forename: Joana
authors.initials: J
authors.lastname: Machado-Santos
authors.forename: Simone
authors.initials: S
authors.lastname: Mader
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Ellwart
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Misu
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wekerle
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, Vienna A-1090, Austria. monika.bradl@meduniwien.ac.at.
authors.forename: Monika
authors.initials: M
authors.lastname: Bradl
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001253:Astrocytes / Q000276:immunology / Q000473:pathology; D001921:Brain / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D009471:Neuromyelitis Optica / Q000276:immunology* / Q000473:pathology; D011917:Rats, Inbred Lew; D017452:Receptors, IgG / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology*
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; C508636:Fcgr2a protein, rat; D007074:Immunoglobulin G; D017452:Receptors, IgG; D007371:Interferon-gamma