Department of Pathology, University of Massachusetts Medical School Worcester, MA, USA.
Front Immunol. 2012 Mar 29;3:64. doi: 10.3389/fimmu.2012.00064. eCollection 2012.
A growing body of evidence suggests that autoreactive CD8 T cells contribute to the disease process in multiple sclerosis (MS). Lymphocytes in MS plaques are biased toward the CD8 lineage, and MS patients harbor CD8 T cells specific for multiple central nervous system (CNS) antigens. Currently, there are relatively few experimental model systems available to study these pathogenic CD8 T cells in vivo. However, the few studies that have been done characterizing the mechanisms used by CD8 T cells to induce CNS autoimmunity indicate that several of the paradigms of how CD4 T cells mediate CNS autoimmunity do not hold true for CD8 T cells or for patients with MS. Thus, myelin-specific CD4 T cells are likely to be one of several important mechanisms that drive CNS disease in MS patients. The focus of this review is to highlight the current models of pathogenic CNS-reactive CD8 T cells and the molecular mechanisms these lymphocytes use when causing CNS inflammation and damage. Understanding how CNS-reactive CD8 T cells escape tolerance induction and induce CNS autoimmunity is critical to our ability to propose and test new therapies for MS.
越来越多的证据表明，自身反应性 CD8 T 细胞有助于多发性硬化症（MS）的疾病进程。MS 斑块中的淋巴细胞偏向于 CD8 谱系，MS 患者体内存在针对多个中枢神经系统（CNS）抗原的 CD8 T 细胞。目前，用于研究体内这些致病性 CD8 T 细胞的实验模型系统相对较少。然而，已经进行了少数几项研究来描述 CD8 T 细胞诱导中枢神经系统自身免疫的机制，这些研究表明，CD4 T 细胞介导中枢神经系统自身免疫的几种范例并不适用于 CD8 T 细胞或 MS 患者。因此，髓鞘特异性 CD4 T 细胞可能是驱动 MS 患者中枢神经系统疾病的几种重要机制之一。本综述的重点是强调致病性中枢神经系统反应性 CD8 T 细胞的当前模型，以及这些淋巴细胞在引起中枢神经系统炎症和损伤时使用的分子机制。了解中枢神经系统反应性 CD8 T 细胞如何逃避耐受诱导并诱导中枢神经系统自身免疫，对于我们提出和测试 MS 的新疗法至关重要。
