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Pohl, M.* ; Kawakami, N.* ; Kitic, M.* ; Bauer, J.* ; Martins, R.* ; Fischer, M.T.* ; Machado-Santos, J.* ; Mader, S.* ; Ellwart, J.W. ; Misu, T.* ; Fujihara, K.* ; Wekerle, H.* ; Reindl, M.* ; Lassmann, H.* ; Bradl, M.*

T cell-activation in neuromyelitis optica lesions plays a role in their formation.

Acta Neuropathol. Commun. 1:85 (2013)
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ACKGROUND: 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Aquaporin 4 ; Ifn-γ ; Lesion ; Neuromyelitis Optica ; T Cell Activation
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 0
e-ISSN 2051-5960
Zeitschrift Acta Neuropathologica Communications
Quellenangaben Band: 1, Heft: 1, Seiten: , Artikelnummer: 85 Supplement: ,
Verlag BioMed Central
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501793-001
PubMed ID 24367907
DOI 10.1186/2051-5960-1-85
Scopus ID 85005777594
Erfassungsdatum 2014-01-27
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