Pathogenic aquaporin-4 reactive T cells are sufficient to induce mouse model of neuromyelitis optica.
Pathogenic aquaporin-4 reactive T cells are sufficient to induce mouse model of neuromyelitis optica.
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DOI：
10.1186/s40478-015-0207-1
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发表时间：
2015-05-21
影响因子：
7.1
通讯作者：
Levy M
中科院分区：
文献类型：
--
作者：
Jones MV;Huang H;Calabresi PA;Levy M
视神经脊髓炎(NMO)是一种自身免疫性疾病，主要发生在脊髓和视神经，导致瘫痪和失明。在大多数患者中发现了针对星形细胞水通道AQP4(AQP4)的抗体，从而推测该抗体在疾病发病机制中是必要的。然而，T细胞在中枢神经系统中的潜在作用还没有得到彻底的研究。我们用致病的AQP4反应性T细胞免疫AQP4缺失的小鼠，建立了抗AQP4抗体血清阴性的NMO模型，方法是用AQP4第二细胞外环C环的多肽免疫AQP4缺失的小鼠，当极化到Th17表型并转移到野生型小鼠时，这些细胞会导致尾部和四肢无力。组织学检查显示脊髓、视神经和脑内有脱髓鞘和T细胞浸润。在培养中接受非特异性蛋白再次刺激的细胞的动物没有出现行为疾病，这表明AQP4的特异性靶向对这种表型至关重要。综上所述，我们发现AQP4反应性T细胞足以在小鼠中引发NMO样疾病，而不依赖抗体，这表明致病的AQP4反应性T细胞可能在人类中发挥类似的作用。
Neuromyelitis Optica (NMO) is an autoimmune disease primarily targeting the spinal cord and optic nerve leading to paralysis and blindness. The discovery of an antibody against the astrocytic water channel, aquaporin-4 (AQP4), in the majority of patients, has led to the presumption that the antibody was necessary for disease pathogenesis. The potential role of T cells in the central nervous system, however, has not been thoroughly examined. We generated an anti-AQP4 antibody seronegative model of NMO using pathogenic AQP4-reactive T cells in mice by immunizing AQP4 null mice with peptides corresponding to the second extracellular loop of AQP4, loop C. When polarized to a Th17 phenotype and transferred to wild-type mice, these cells caused tail and limb weakness. Histology showed demyelination and T cell infiltration in the spinal cord, optic nerve and brain. Animals receiving cells re-stimulated in culture with non-specific proteins resulted in no behavioral disease, indicating that specific targeting of AQP4 is essential for this phenotype. In summary, we show that AQP4-reactive T cells are sufficient to trigger an NMO-like disease in mice, independent of antibodies, indicating that pathogenic AQP4-reactive T cells may play a similar role in humans.
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影响因子：
11.2
作者：
Bennett, Jeffrey L.;Lam, Chiwah;Kalluri, Sudhakar Reddy;Saikali, Philippe;Bautista, Katherine;Dupree, Cecily;Glogowska, Magdalena;Case, David;Antel, Jack P.;Owens, Gregory P.;Gilden, Don;Nessler, Stefan;Stadelmann, Christine;Hemmer, Bernhard
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影响因子：
6.4
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通讯作者：
Verkman, A. S.
DOI：
10.1016/j.bbrc.2010.02.157
发表时间：
2010-03-26
影响因子：
3.1
作者：
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通讯作者：
Sakoda, Saburo
影响因子：
5.8
作者：
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