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SHR Neuro Cancer Cardio Lipid Metab Microb

Zeka, B; Hastermann, M; Hochmeister, S; Kögl, N; Kaufmann, N; Schanda, K; Mader, S; Misu, T; Rommer, P; Fujihara, K; Illes, Z; Leutmezer, F; Sato, DK; Nakashima, I; Reindl, M; Lassmann, H; Bradl, M.
Highly encephalitogenic aquaporin 4-specific T cells and NMO-IgG jointly orchestrate lesion location and tissue damage in the CNS.
Acta Neuropathol. 2015; 130(6):783-798 Doi: 10.1007/s00401-015-1501-5 [OPEN ACCESS]
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Co-authors Med Uni Graz: Hochmeister Sonja
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Abstract:: In neuromyelitis optica (NMO), astrocytes become targets for pathogenic aquaporin 4 (AQP4)-specific antibodies which gain access to the central nervous system (CNS) in the course of inflammatory processes. Since these antibodies belong to a T cell-dependent subgroup of immunoglobulins, and since NMO lesions contain activated CD4(+) T cells, the question arose whether AQP4-specific T cells might not only provide T cell help for antibody production, but also play an important role in the induction of NMO lesions. We show here that highly pathogenic, AQP4-peptide-specific T cells exist in Lewis rats, which recognize AQP4268-285 as their specific antigen and cause severe panencephalitis. These T cells are re-activated behind the blood-brain barrier and deeply infiltrate the CNS parenchyma of the optic nerves, the brain, and the spinal cord, while T cells with other AQP4-peptide specificities are essentially confined to the meninges. Although AQP4268-285-specific T cells are found throughout the entire neuraxis, they have NMO-typical "hotspots" for infiltration, i.e. periventricular and periaqueductal regions, hypothalamus, medulla, the dorsal horns of spinal cord, and the optic nerves. Most remarkably, together with NMO-IgG, they initiate large astrocyte-destructive lesions which are located predominantly in spinal cord gray matter. We conclude that the processing of AQP4 by antigen presenting cells in Lewis rats produces a highly encephalitogenic AQP4 epitope (AQP4268-285), that T cells specific for this epitope are found in the immune repertoire of normal Lewis rats and can be readily expanded, and that AQP4268-285-specific T cells produce NMO-like lesions in the presence of NMO-IgG.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Aquaporin 4 - genetics; Aquaporin 4 - metabolism; Astrocytes - immunology; Astrocytes - pathology; Cell Line -; Central Nervous System - immunology; Central Nervous System - pathology; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Humans -; Immunoglobulin G - immunology; Interferon-gamma - metabolism; Interleukin-17 - metabolism; Neuromyelitis Optica - immunology; Neuromyelitis Optica - pathology; Optic Nerve - immunology; Optic Nerve - pathology; Rats, Inbred Lew -; T-Lymphocytes - metabolism; T-Lymphocytes - pathology
Find related publications in this database (Keywords): CNS inflammation; Neuromyelitis optica; T cells; Aquaporin 4; ENMO