Immunopathogenesis of multiple sclerosis: new insights and therapeutic implications.
Immunopathogenesis of multiple sclerosis: new insights and therapeutic implications.
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DOI：
10.1212/01.con.0000389940.92283.aa
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发表时间：
2010-10-01
期刊：
影响因子：
--
通讯作者：
Stuve, Olaf
中科院分区：
文献类型：
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作者：
Awad, Amer M;Stuve, Olaf
多发性硬化症(MS)是一种中枢神经系统炎症性、脱髓鞘和神经退行性疾病。多发性硬化症的病因尚不清楚。然而，免疫失调在这种疾病的神经发病机制中起着关键作用，这是公认的。在本文中，我们讨论了目前关于MS免疫发病机制中复杂的细胞和分子相互作用的假说，尽管CD4T淋巴细胞长期以来一直被认为是MS免疫病理中的关键细胞因子，但最近也对其他细胞类型的作用进行了研究。在MS皮损中，CD_4和CD_8细胞的空间分布明显不同。另一个T淋巴细胞亚群-的T细胞亚群流行的学说认为，CD4辅助T(TH)1型细胞释放导致组织损伤的细胞因子和炎症介质，而CD4TH2细胞可能参与了这些影响的调节。然而，越来越多的证据表明，额外的T细胞亚群，包括TH17细胞、CD8效应T细胞和CD4CD25调节性T细胞，也会影响疾病的活动性。此外，关于B淋巴细胞和其他抗原提呈细胞在MS神经发病机制中的突出作用的临床和副临床数据正在积累中。鉴于这些观察，针对多发性硬化症的新的治疗干预措施将需要专注于重置免疫系统的多个组成部分。
Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disorder of the CNS. The etiology of MS remains unknown. However, it is well established that immune dysregulation plays a critical role in the neuropathogenesis of this disorder. In this review, we discuss the current hypotheses concerning the complex cellular and molecular interactions involved in the immunopathogenesis of MS. Although CD4 T lymphocytes have long been considered the critical cellular factor in the immunopathology of MS, the role of other cell types has also recently been investigated. It appears that the spatial distribution of CD4 and CD8 cells in MS lesions is distinct. Yet another T-lymphocyte subset, gamma/delta T cells, can be detected in very early MS lesions. The prevalent dogma suggests that CD4 helper T (TH) type 1 cells release cytokines and inflammatory mediators that cause tissue damage, while CD4 TH2 cells might be involved in modulation of these effects. However, a mounting body of evidence suggests that additional T-cell subsets, including TH17 cells, CD8 effector T cells, and CD4 CD25 regulatory T cells, also affect disease activity. In addition, clinical and paraclinical data are accumulating on the prominent role of B lymphocytes and other antigen-presenting cells in MS neuropathogenesis. Given these observations, new therapeutic interventions for MS will need to focus on resetting multiple components of the immune system.