Protective and detrimental roles for regulatory T cells in a viral model for multiple sclerosis.
Protective and detrimental roles for regulatory T cells in a viral model for multiple sclerosis.
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DOI：
10.1111/bpa.12119
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Tsunoda I
中科院分区：
文献类型：
--
作者：
Martinez NE;Karlsson F;Sato F;Kawai E;Omura S;Minagar A;Grisham MB;Tsunoda I
多发性硬化症（MS）被认为是一种由病毒感染引发的免疫介导的中枢神经系统（CNS）疾病。在Theiler小鼠脑脊髓炎病毒（TMEV）感染中，在第一周（急性期），小鼠发生脊髓灰质炎脑脊髓炎。3周后（慢性期），小鼠出现病毒持续存在的免疫介导的脱髓鞘，这已被用作ms的病毒模型，调节性T细胞（Regulatory T cells, Tregs）可以抑制炎症，并被认为对免疫介导的疾病（包括ms）具有保护作用。然而，在病毒诱导的炎症性脱髓鞘中，Tregs虽然可以抑制炎症，防止免疫介导的病理，但Tregs也可能抑制抗病毒免疫反应。导致更活跃的病毒复制和/或持久性。为了确定Tregs在MS中的作用和潜在的翻译用途，我们在tmev感染小鼠的第0天（早期）或慢性期（治疗期）用体外产生的诱导Tregs （iTregs）治疗。急性期早期治疗加重临床症状。急性疾病的恶化与病毒滴度增加和中枢神经系统免疫细胞募集减少有关。治疗性iTreg治疗可减少慢性疾病期间的炎症性脱髓鞘。免疫方面，iTreg治疗增加了B细胞、CD4+ T细胞和树突状细胞产生的白细胞介素-10，这可能有助于减少中枢神经系统炎症。
Multiple sclerosis (MS) has been proposed to be an immune-mediated disease in the central nervous system (CNS) that can be triggered by virus infections. In Theiler’s murine encephalomyelitis virus (TMEV) infection, during the first week (acute stage), mice develop polioencephalomyelitis. After 3 weeks (chronic stage), mice develop immune-mediated demyelination with virus persistence, which has been used as a viral model for MS. Regulatory T cells (Tregs) can suppress inflammation, and have been suggested to be protective in immune-mediated diseases, including MS. However, in virus-induced inflammatory demyelination, although Tregs can suppress inflammation, preventing immune-mediated pathology, Tregs may also suppress anti-viral immune responses, leading to more active viral replication and/or persistence. To determine the role and potential translational usage of Tregs in MS, we treated TMEV-infected mice with ex vivo-generated induced Tregs (iTregs) on day 0 (early) or during the chronic stage (therapeutic). Early treatment worsened clinical signs during acute disease. The exacerbation of acute disease was associated with increased virus titers and decreased immune cell recruitment in the CNS. Therapeutic iTreg treatment reduced inflammatory demyelination during chronic disease. Immunologically, iTreg treatment increased interleukin-10 production from B cells, CD4+ T cells, and dendritic cells, which may contribute to the decreased CNS inflammation.
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DOI：
10.1084/jem.20051166
发表时间：
2005-12-05
期刊：
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影响因子：
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DOI：
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发表时间：
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发表时间：
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期刊：
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影响因子：
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DOI：
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发表时间：
1997-08-04
期刊：
The Journal of experimental medicine
影响因子：
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DOI：
10.1007/978-1-61737-979-6_2
发表时间：
2011
期刊：
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影响因子：
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