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

Maria Pohl, Naoto Kawakami, Maja Kitic, Jan Bauer, Rui Martins, Marie Therese Fischer, Joana Machado-Santos, Simone Mader, Joachim W. Ellwart, Tatsuro Misu, Kazuo Fujihara, Hartmut Wekerle, Markus Reindl, Hans Lassmann, Monika Bradl

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

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.

Original languageEnglish
Article number85
JournalActa Neuropathologica Communications
Volume2
Issue number1
DOIs
Publication statusPublished - 2014 Jan 27

Keywords

  • Aquaporin 4
  • IFN-γ
  • Lesion
  • Neuromyelitis optica
  • T cell activation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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