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
- 巻
- 130
- 号
- 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
- 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