論文

査読有り
2015年12月

Highly encephalitogenic aquaporin 4-specific T cells and NMO-IgG jointly orchestrate lesion location and tissue damage in the CNS

ACTA NEUROPATHOLOGICA
  • Bleranda Zeka
  • Maria Hastermann
  • Sonja Hochmeister
  • Nikolaus Koegl
  • Nathalie Kaufmann
  • Kathrin Schanda
  • Simone Mader
  • Tatsuro Misu
  • Paulus Rommer
  • Kazuo Fujihara
  • Zsolt Illes
  • Fritz Leutmezer
  • Douglas Kazutoshi Sato
  • Ichiro Nakashima
  • Markus Reindl
  • Hans Lassmann
  • Monika Bradl
  • 全て表示

130
6
開始ページ
783
終了ページ
798
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00401-015-1501-5
出版者・発行元
SPRINGER

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 AQP4(268-285) 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 AQP4(268-285)-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 (AQP4(268-285)), that T cells specific for this epitope are found in the immune repertoire of normal Lewis rats and can be readily expanded, and that AQP4(268-285)-specific T cells produce NMO-like lesions in the presence of NMO-IgG.

リンク情報
DOI
https://doi.org/10.1007/s00401-015-1501-5
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26530185
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000365304900003&DestApp=WOS_CPL
ID情報
  • DOI : 10.1007/s00401-015-1501-5
  • ISSN : 0001-6322
  • eISSN : 1432-0533
  • PubMed ID : 26530185
  • Web of Science ID : WOS:000365304900003

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