Immune tolerance in multiple sclerosis.
Immune tolerance in multiple sclerosis.
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DOI：
10.1111/j.1600-065x.2011.01016.x
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发表时间：
2011-05
影响因子：
8.7
通讯作者：
Goverman JM
中科院分区：
文献类型：
--
作者：
Goverman JM
多发性硬化症被认为是由髓鞘抗原特异性的T细胞介导的，这些T细胞在健康个体的周围无害地循环，直到它们被环境刺激错误地感染。激活后，T细胞进入中枢神经系统，并协调针对髓磷脂的免疫反应。为了了解多发性硬化症发病机制的最初步骤，重要的是要确定维持T细胞对髓磷脂抗原耐受性的机制，并了解一些髓磷脂特异性T细胞如何逃避耐受性以及什么条件导致它们被激活。中枢耐受强烈塑造髓磷脂特异性T细胞的外周库，因为大多数髓磷脂特异性T细胞通过胸腺的克隆缺失被消除。逃避中心耐受的自反应性T细胞通常只能与抗原呈递细胞进行低强度的相互作用。尽管这些相互作用的发生率较低，但需要外周耐受机制来防止自发自身免疫。髓磷脂特异性T细胞的多种外周耐受机制已经被确定，其中最重要的似乎是调节性T细胞。虽然大多数研究都集中在CD4+髓磷脂特异性T细胞上，但最近对CD8+髓磷脂特异性T细胞耐受性机制和消除这些机制的条件的有趣差异进行了描述。
Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T-cell tolerance to myelin antigens and to understand how some myelin-specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin-specific T cells, as most myelin-specific T cells are eliminated by clonal deletion in the thymus. Self-reactive T cells that escape central tolerance are generally capable only of low-avidity interactions with antigen-presenting cells. Despite the low avidity of these interactions, peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms for myelin-specific T cells have been indentified, the most important of which appears to be regulatory T cells. While most studies have focused on CD4+ myelin-specific T cells, interesting differences in tolerance mechanisms and the conditions that abrogate these mechanisms have recently been described for CD8+ myelin-specific T cells.