Wu Gregory F, Laufer Terri M
Department of Neurology, Hospital of the University of Pennsylvania, 745 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Curr Neurol Neurosci Rep. 2007 May;7(3):245-52. doi: 10.1007/s11910-007-0037-z.
Although multiple sclerosis (MS) is a presumed T-cell- mediated disease, it is unclear what triggers the development of neuroantigen-specific T cells. Autoreactive CD4(+) T cells are activated by antigen presenting cells; dendritic cells (DCs) are the primary antigen presenting cells directing T-cell functions and are, therefore, extremely important in directing the immune pathology characteristic of MS. Three important concepts have emerged regarding DCs in MS. First, DCs are present within the healthy central nervous system (CNS) in association with the cerebrospinal fluid space and microvasculature. Therefore, the potential for sampling of CNS antigens in similar fashion to other tissues and organs exists and likely plays an integral role in CNS immunity. The degree of involvement, as well as the source, of these CNS DCs has been addressed by several studies using the experimental autoimmune encephalomyelitis animal model. Second, DCs are found within MS lesions and have been shown to be functionally abnormal in patients with MS. Lastly, therapeutics directed at DCs could potentially be engineered for treatment in MS and in fact may already be involved in the mechanisms of current immunomodulatory therapies.
尽管多发性硬化症（MS）被认为是一种由T细胞介导的疾病，但尚不清楚是什么触发了神经抗原特异性T细胞的发育。自身反应性CD4(+) T细胞由抗原呈递细胞激活；树突状细胞（DCs）是指导T细胞功能的主要抗原呈递细胞，因此在指导MS的免疫病理学特征方面极为重要。关于MS中DCs出现了三个重要概念。首先，DCs存在于健康的中枢神经系统（CNS）中，与脑脊液间隙和微脉管系统相关。因此，存在以与其他组织和器官类似的方式对CNS抗原进行采样的可能性，并且这可能在CNS免疫中发挥不可或缺的作用。几项使用实验性自身免疫性脑脊髓炎动物模型的研究已经探讨了这些CNS DCs的参与程度以及来源。其次，在MS病变中发现了DCs，并且已证明它们在MS患者中功能异常。最后，针对DCs的治疗方法有可能被设计用于MS的治疗，实际上可能已经参与了当前免疫调节疗法的机制。
