Tompkins S Mark, Fuller Kevin G, Miller Stephen D
Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Ann N Y Acad Sci. 2002 Apr;958:26-38.
Theiler's murine encephalomyelitis virus (TMEV), a natural mouse pathogen, is a neurotropic picornavirus that induces a chronic, CD4+ T cell-mediated demyelinating disease with a clinical course and histopathology similar to those of chronic-progressive multiple sclerosis. Upon infection, TMEV-specific CD4+ T cells target persistent viral antigens in the CNS and initiate myelin damage. Later in the disease, myelin-specific CD4+ T cells are primed by epitope spreading, and these autoimmune T cells contribute to the pathogenesis of the chronic-progressive disease. This review focuses upon aspects of the initiation of a virally induced CD4+ T cell-mediated autoimmune response. First, the steps involved in the hierarchical activation of non-cross-reactive myelin-specific T cells in the SJL/J mouse after CNS infection with TMEV and the role of these autoreactive T cells in chronic myelin damage are discussed. Second, the process of epitope spreading and the role of CNS antigen presenting cells in the temporal presentation of self-antigens is considered. Finally, we will discuss aspects of T cell activation and antigen presentation, and how they can impact autoimmune disease.
泰勒氏鼠脑脊髓炎病毒（TMEV）是一种天然的小鼠病原体，是一种嗜神经性微小核糖核酸病毒，可引发一种慢性的、由CD4 + T细胞介导的脱髓鞘疾病，其临床病程和组织病理学与慢性进行性多发性硬化症相似。感染后，TMEV特异性CD4 + T细胞靶向中枢神经系统中持续存在的病毒抗原并引发髓鞘损伤。在疾病后期，髓鞘特异性CD4 + T细胞通过表位扩展被激活，这些自身免疫性T细胞促成了慢性进行性疾病的发病机制。本综述聚焦于病毒诱导的CD4 + T细胞介导的自身免疫反应起始的各个方面。首先，讨论了SJL/J小鼠在感染TMEV后中枢神经系统中未交叉反应的髓鞘特异性T细胞分级激活所涉及的步骤，以及这些自身反应性T细胞在慢性髓鞘损伤中的作用。其次，考虑了表位扩展过程以及中枢神经系统抗原呈递细胞在自身抗原的适时呈递中的作用。最后，我们将讨论T细胞激活和抗原呈递的各个方面，以及它们如何影响自身免疫性疾病。
