Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT 84132, USA.
J Neurovirol. 2012 Feb;18(1):45-54. doi: 10.1007/s13365-012-0077-2. Epub 2012 Jan 27.
Major histocompatibility complex class I-restricted CD8(+) cytotoxic T lymphocytes are involved in the pathogenesis of multiple sclerosis (MS) and both autoimmune, experimental autoimmune encephalomyelitis, and viral, Theiler's murine encephalomyelitis virus (TMEV) infection, animal models of MS. Following TMEV infection, certain T cell hybridomas, generated from cloned TMEV-induced CD8(+) T cells, were able to produce clinical signs of disease (flaccid hind limb paralysis) upon adoptive transfer into naive mice. Dual T cell receptors (TCR) are present on the surface of these cells as both Vβ3 and Vβ6 were detected by polymerase chain reaction (PCR) screening and flow cytometry and multiple Vα mRNAs were detected by PCR screening. This is the first demonstration of antiviral CD8(+) T cells having more than one TCR initiating an autoimmune disease in the natural host of the virus. We hypothesize that this is a potential mechanism for virus-induced autoimmune disease initiated by CD8(+) T cells.
主要组织相容性复合体 I 类限制性 CD8(+)细胞毒性 T 淋巴细胞参与多发性硬化症 (MS) 的发病机制，包括自身免疫、实验性自身免疫性脑脊髓炎和病毒，如 Theiler 鼠脑脊髓炎病毒 (TMEV) 感染，MS 的动物模型。在 TMEV 感染后，从克隆的 TMEV 诱导的 CD8(+) T 细胞中产生的某些 T 细胞杂交瘤，在过继转移到未感染的小鼠后，能够产生疾病的临床症状（弛缓性后肢瘫痪）。这些细胞表面存在双 T 细胞受体 (TCR)，因为通过聚合酶链反应 (PCR) 筛选和流式细胞术检测到 Vβ3 和 Vβ6，并且通过 PCR 筛选检测到多个 Vα mRNAs。这是首次证明抗病毒 CD8(+) T 细胞具有多于一个 TCR，在病毒的天然宿主中引发自身免疫性疾病。我们假设这是 CD8(+) T 细胞引发病毒诱导的自身免疫性疾病的潜在机制。
