CD8+T cells directed against a viral peptide contribute to loss of motor function by disrupting axonal transport in a viral model of fulminant demyelination
CD8+T cells directed against a viral peptide contribute to loss of motor function by disrupting axonal transport in a viral model of fulminant demyelination
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DOI：
10.1016/j.jneuroim.2007.04.005
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发表时间：
2007-08-01
影响因子：
3.3
通讯作者：
Rodriguez, Moses
中科院分区：
文献类型：
--
作者：
Howe, Charles L.;Ure, Daren;Rodriguez, Moses
脱髓鞘是多发性硬化症的病理特征，可能是与多发性硬化症相关的运动功能障碍的必要条件，但不是充分条件。我们倾向于多发性硬化症的神经退行性模型，并认为去环化创造了一个允许的环境，在这种环境中，剥离的轴突变得容易受到免疫介导的损伤。不幸的是，导致这种轴突损伤的细胞效应器目前尚不清楚。基于先前关于细胞毒性T细胞参与这种损伤的观察，我们评估了在干扰素-γ受体缺陷的急性脱髓鞘小鼠模型中，免疫优势的CD8+抗病毒T细胞反应的肽耗尽后的运动功能、轴突脱落和轴突损伤。我们发现，在感染泰勒氏小鼠脑脊髓炎病毒之前，有针对性地清除这种细胞毒效应细胞，在感染后45天，运动功能得到了实质性的保存，这与脊髓内存活轴突的亚群中逆行轴突运输的保存有关。我们得出结论，细胞毒性T细胞可能是脱髓鞘后轴突损伤的始动因素。(C)2007 Elsevier B.V.保留所有权利。
Demyelination, a pathological hallmark of multiple sclerosis, may be a necessary but not a sufficient condition for motor dysfunction associated with this disease. We favor a neurodegenerative model of multiple sclerosis and suggest that demyclination creates a permissive environment wherein the denuded axon becomes susceptible to immune-mediated injury. Unfortunately, the cellular effectors responsible for eliciting such axonal injury are currently unknown. Based on previous observations implicating cytotoxic T cells in this injury, we assessed motor function, axon dropout, and axon injury following peptide depletion of the immunodominant CD8+ antiviral T cell response in the IFN-y receptordeficient mouse model of acute demyelination. We found that the targeted removal of this population of cytotoxic effector cells prior to infection with the Theiler's murine encephalomyelitis virus caused a substantial preservation of motor function at 45 days postinfection that was associated with preservation of retrograde axonal transport in a subpopulation of surviving axons within the spinal cord. We conclude that cytotoxic T cells may be responsible for the initiation of axon injury following demyelination. (c) 2007 Elsevier B.V. All rights reserved.