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多发性硬化症及其动物模型中的致脑炎性和调节性CD8 T细胞

Encephalitogenic and Regulatory CD8 T Cells in Multiple Sclerosis and Its Animal Models.

作者信息

Mockus Taryn E, Munie Ashley, Atkinson Jeffrey R, Segal Benjamin M

机构信息

Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH 43210.

Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and.

出版信息

J Immunol. 2021 Jan 1;206(1):3-10. doi: 10.4049/jimmunol.2000797.

DOI:10.4049/jimmunol.2000797
PMID:33443060
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7814469/
Abstract

Multiple sclerosis (MS), a neuroinflammatory disease that affects millions worldwide, is widely thought to be autoimmune in etiology. Historically, research into MS pathogenesis has focused on autoreactive CD4 T cells because of their critical role in the animal model, experimental autoimmune encephalomyelitis, and the association between MS susceptibility and single-nucleotide polymorphisms in the MHC class II region. However, recent studies have revealed prominent clonal expansions of CD8 T cells within the CNS during MS. In this paper, we review the literature on CD8 T cells in MS, with an emphasis on their potential effector and regulatory properties. We discuss the impact of disease modifying therapies, currently prescribed to reduce MS relapse rates, on CD8 T cell frequency and function. A deeper understanding of the role of CD8 T cells in MS may lead to the development of more effective and selective immunomodulatory drugs for particular subsets of patients.

摘要

多发性硬化症(MS)是一种影响全球数百万人的神经炎症性疾病,病因上普遍认为是自身免疫性的。从历史上看,由于自身反应性CD4 T细胞在动物模型实验性自身免疫性脑脊髓炎中的关键作用,以及MS易感性与MHC II类区域单核苷酸多态性之间的关联,对MS发病机制的研究一直集中在这些细胞上。然而,最近的研究表明,在MS病程中,中枢神经系统内CD8 T细胞出现了显著的克隆性扩增。在本文中,我们综述了关于MS中CD8 T细胞的文献,重点关注它们潜在的效应和调节特性。我们讨论了目前用于降低MS复发率的疾病修饰疗法对CD8 T细胞频率和功能的影响。更深入地了解CD8 T细胞在MS中的作用可能会为特定患者亚群开发出更有效、更具选择性的免疫调节药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9166/7814469/e292a15e39d7/nihms-1625045-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9166/7814469/e292a15e39d7/nihms-1625045-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9166/7814469/e292a15e39d7/nihms-1625045-f0001.jpg

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本文引用的文献

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Effect of dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis.富马酸二甲酯对复发型多发性硬化症患者淋巴细胞亚群的影响。
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Tissue-resident memory T cells invade the brain parenchyma in multiple sclerosis white matter lesions.组织驻留记忆 T 细胞浸润多发性硬化症白质病变的脑组织。
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Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis.
治疗初发多发性硬化症患者脑脊液的靶向蛋白质组学鉴定出临床表型的免疫生物标志物。
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2-Bromo-1,4-Naphthalenedione promotes CD8 T cell expansion and limits Th1/Th17 to mitigate experimental autoimmune encephalomyelitis.2-溴-1,4-萘二酮促进 CD8 T 细胞扩增并限制 Th1/Th17 细胞,从而减轻实验性自身免疫性脑脊髓炎。
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Ursolic acid derivative UAOS-Na treats experimental autoimmune encephalomyelitis by immunoregulation and protecting myelin.熊果酸衍生物UAOS-Na通过免疫调节和保护髓鞘来治疗实验性自身免疫性脑脊髓炎。
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CD8+ T cells recognizing a neuron-restricted antigen injure axons in a model of multiple sclerosis.CD8+ T 细胞识别神经元限制性抗原损伤多发性硬化模型中的轴突。
J Clin Invest. 2023 Nov 1;133(21):e162788. doi: 10.1172/JCI162788.
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