Karpus W J, Pope J G, Peterson J D, Dal Canto M C, Miller S D
Department of Microbiology, Northwestern University Medical School, Chicago, IL 60611, USA.
J Immunol. 1995 Jul 15;155(2):947-57.
Theiler's murine encephalomyelitis virus (TMEV), a member of the cardiovirus subfamily of the Picornaviridae, is a natural pathogen of mice. Thirty to 60 days following intracerebral infection with TMEV, susceptible inbred mouse strains develop a chronic, progressive, T cell-mediated inflammatory demyelinating disease of the central nervous system (CNS) characterized by spastic hind limb paralysis and a lifelong persistent CNS virus infection. We have examined the effect of peripheral virus-specific tolerance on the development of demyelinating disease. Treatment of SJL/J mice with TMEV-coupled, ethyl carbodiimide-treated splenocytes either before or after infection with live TMEV prevented the development of clinical disease, including inflammation and demyelination in the CNS. Prevention of clinical disease was paralleled by significant reductions in virus-specific immune responses, including delayed type hypersensitivity and T cell proliferative responses. Tolerance induction resulted in a significant reduction in the absolute numbers of mononuclear cells infiltrating the CNS, particularly the CD4+IL-2R+ T cell subset, 3, 5, and 8 wk postinfection. In contrast, tolerance induction had no effect on the numbers of CD8+IL-2R+ T cells infiltrating the CNS. Treatment with TMEV-coupled splenocytes failed to prevent the development of relapsing experimental autoimmune encephalomyelitis, demonstrating the specificity of in vivo tolerance induction. Prevention of demyelinating disease did not correlate with the increased TMEV-specific Ab responses observed in tolerized mice. These results indicate that induction of immune tolerance to TMEV can down-regulate a chronic immunopathogenic disease directed against virus Ag persisting in the CNS that normally results in a progressive demyelinating disease similar to multiple sclerosis.
泰勒氏鼠脑脊髓炎病毒（TMEV）是小核糖核酸病毒科心病毒亚科的成员，是小鼠的天然病原体。用TMEV脑内感染后30至60天，易感近交系小鼠品系会发生一种慢性、进行性、T细胞介导的中枢神经系统（CNS）炎性脱髓鞘疾病，其特征为后肢痉挛性麻痹和终身持续的CNS病毒感染。我们研究了外周病毒特异性耐受对脱髓鞘疾病发展的影响。在用活TMEV感染之前或之后，用TMEV偶联的、经碳二亚胺处理的脾细胞治疗SJL/J小鼠，可预防临床疾病的发展，包括CNS中的炎症和脱髓鞘。临床疾病的预防与病毒特异性免疫反应的显著降低平行，包括迟发型超敏反应和T细胞增殖反应。耐受诱导导致感染后3、5和8周浸润CNS的单核细胞绝对数量显著减少，尤其是CD4+IL-2R+T细胞亚群。相比之下，耐受诱导对浸润CNS的CD8+IL-2R+T细胞数量没有影响。用TMEV偶联的脾细胞治疗未能预防复发性实验性自身免疫性脑脊髓炎的发展，证明了体内耐受诱导的特异性。脱髓鞘疾病的预防与在耐受小鼠中观察到的TMEV特异性抗体反应增加无关。这些结果表明，对TMEV诱导免疫耐受可下调针对持续存在于CNS中的病毒抗原的慢性免疫致病疾病，该疾病通常会导致类似于多发性硬化症的进行性脱髓鞘疾病。
