Effector T Cells in Multiple Sclerosis
Effector T Cells in Multiple Sclerosis
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DOI：
10.1101/cshperspect.a029025
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发表时间：
2018-04-01
影响因子：
5.4
通讯作者：
Baecher-Allan, Clare
中科院分区：
文献类型：
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作者：
Kaskow, Belinda J.;Baecher-Allan, Clare
多发性硬化症(MS)长期以来一直被认为是一种CD4T细胞疾病，主要是因为发现MS的最大遗传风险是主要组织相容性复合体(MHC)II类基因座，并且T细胞在指导免疫反应中发挥核心作用。最近的临床试验数据显示，Th1/Th17细胞在中枢神经系统(CNS)组织、脑脊液(CSF)和血液中的存在增加，以及对MS动物模型(如实验性自身免疫性脑脊髓炎(EAE))的研究表明，辅助性T细胞(Th)1细胞因子干扰素-伽马(IFN-γ)和Th17细胞因子IL-17在MS发病机制中的重要性。虽然大多数关于MS发病机制的研究都集中在效应分子CD4T细胞的作用上，但越来越多的数据表明CD8T细胞在人类疾病中可能起着重要的作用。事实上，与大多数动物模型相比，在MS患者的中枢神经系统中发现的主要T细胞是CD8T细胞。由于患者来源的效应性T细胞也抵抗显性耐受机制，如与调节性T细胞(Treg)的相互作用，它们对调节的反应降低也可能导致MS患者的效应性T细胞活性不受抑制。这些概念将在下面讨论。
Multiple sclerosis (MS) has long been considered a CD4 T-cell disease, primarily because of the findings that the strongest genetic risk for MS is the major histocompatibility complex (MHC) class II locus, and that T cells play a central role in directing the immune response. The importance that the T helper (Th)1 cytokine, interferon gamma (IFN-gamma), and the Th17 cytokine, interleukin (IL)-17, play in MS pathogenesis is indicated by recent clinical trial data by the enhanced presence of Th1/Th17 cells in central nervous system (CNS) tissue, cerebrospinal fluid (CSF), and blood, and by research on animal models of MS, such as experimental autoimmune encephalomyelitis (EAE). Although the majority of research on MS pathogenesis has centered on the role of effector CD4 T cells, accumulating data suggests that CD8 T cells may play a significant role in the human disease. In fact, in contrast to most animal models, the primary T cell found in the CNS in patients with MS, is the CD8 T cell. As patient-derived effector T cells are also resistant to mechanisms of dominant tolerance such as that induced by interaction with regulatory T cells (Tregs), their reduced response to regulation may also contribute to the unchecked effector T-cell activity in patients with MS. These concepts will be discussed below.