title: Pathogenic T cell responses against aquaporin 4.
abstract: Inflammatory lesions in the central nervous system of patients with neuromyelitis optica are characterized by infiltration of T cells and deposition of aquaporin-4-specific antibodies and complement on astrocytes at the glia limitans. Although the contribution of aquaporin-4-specific autoantibodies to the disease process has been recently elucidated, a potential role of aquaporin-4-specific T cells in lesion formation is unresolved. To address this issue, we raised aquaporin-4-specific T cell lines in Lewis rats and characterized their pathogenic potential in the presence and absence of aquaporin-4-specific autoantibodies of neuromyelitis optica patients. We show that aquaporin-4-specific T cells induce brain inflammation with particular targeting of the astrocytic glia limitans and permit the entry of pathogenic anti-aquaporin-4-specific antibodies to induce NMO-like lesions in spinal cord and brain. In addition, transfer of aquaporin-4-specific T cells provoked mild (subclinical) myositis and interstitial nephritis. We further show that the expression of the conformational epitope, recognized by NMO patient-derived aquaporin-4-specific antibodies is induced in kidney cells by the pro-inflammatory cytokine gamma-interferon. Our data provide further support for the view that NMO lesions may be induced by a complex interplay of T cell mediated and humoral immune responses against aquaporin-4.
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, 1090 Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Pohl
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Fischer
authors.forename: Simone
authors.initials: S
authors.lastname: Mader
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schanda
authors.forename: Maja
authors.initials: M
authors.lastname: Kitic
authors.forename: Rakhi
authors.initials: R
authors.lastname: Sharma
authors.forename: Isabella
authors.initials: I
authors.lastname: Wimmer
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Misu
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Monika
authors.initials: M
authors.lastname: Bradl
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000276:immunology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009471:Neuromyelitis Optica / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007371:Interferon-gamma