Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS. Although CD4⁺ T cells are implicated in MS pathogenesis and have been the main focus of MS research using the animal model experimental autoimmune encephalomyelitis (EAE), substantial evidence from patients with MS points to a role for CD8⁺ T cells in disease pathogenesis. We previously showed that an MHC class I–restricted epitope of myelin basic protein (MBP) is presented in the CNS during CD4⁺ T cell–initiated EAE. Here, we investigated whether naive MBP-specific CD8⁺ T cells recruited to the CNS during CD4⁺ T cell–initiated EAE engaged in determinant spreading and influenced disease. We found that the MBP-specific CD8⁺ T cells exacerbated brain but not spinal cord inflammation. We show that a higher frequency of monocytes and monocyte-derived cells presented the MHC class I–restricted MBP ligand in the brain compared with the spinal cord. Infiltration of MBP-specific CD8⁺ T cells enhanced ROS production in the brain only in these cell types and only when the MBP-specific CD8⁺ T cells expressed Fas ligand (FasL). These results suggest that myelin-specific CD8⁺ T cells may contribute to disease pathogenesis via a FasL-dependent mechanism that preferentially promotes lesion formation in the brain.

中文翻译：

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髓鞘特异性CD8 ⁺ T细胞加重中枢神经系统自身免疫性脑炎

多发性硬化症（MS）是CNS的一种炎症性脱髓鞘疾病。尽管CD4 ⁺ T细胞与MS发病机制有关，并且已成为使用动物模型实验性自身免疫性脑脊髓炎（EAE）进行MS研究的主要焦点，但来自MS患者的大量证据表明CD8 ⁺ T细胞在疾病发病机理中的作用。我们以前的研究表明，在CD4 ⁺ T细胞引发的EAE期间，CNS中存在MHC I类限制性髓磷脂碱性蛋白（MBP）的抗原决定簇。在这里，我们调查了在CD4 ⁺ T细胞引发的EAE期间是否将幼稚的MBP特异性CD8 ⁺ T细胞募集到CNS中，从而参与了决定因素的传播并影响了疾病。我们发现特定于MBP的CD8⁺ T细胞可加重大脑，但不会加重脊髓炎症。我们显示，与脊髓相比，单核细胞和单核细胞衍生的细胞在大脑中呈现MHC I类限制性MBP配体的频率更高。MBP特异性CD8 ⁺ T细胞的浸润仅在这些细胞类型中并且仅当MBP特异性CD8 ⁺ T细胞表达Fas配体（FasL）时，才增强大脑中的ROS产生。这些结果表明，髓磷脂特异性CD8 ⁺ T细胞可能通过FasL依赖性机制（其优先促进大脑中病变的形成）促进疾病的发病。