Matsuura Eiji, Kubota Ryuji, Tanaka Yuetsu, Takashima Hiroshi, Izumo Shuji
From the Department of Neurology and Geriatrics (EM, HT) and Center for Chronic Viral Diseases (RK, SI), Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima; and Department of Immunology, University of the Ryukyus, Okinawa (YT), Japan.
J Neuropathol Exp Neurol. 2015 Jan;74(1):2-14. doi: 10.1097/NEN.0000000000000141.
Activated human T-lymphotropic virus type-1 (HTLV-1)-specific CD8-positive cytotoxic T lymphocytes (CTLs) are markedly increased in the periphery of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-1-induced inflammatory disease of the CNS. Although virus-specific CTLs play a pivotal role to eliminate virus-infected cells, the potential role of HTLV-1-specific CTLs in the pathogenesis of HAM/TSP remains unclear. To address this issue, we evaluated the infiltration of HTLV-1-specific CTLs and the expression of HTLV-1 proteins in the spinal cords of 3 patients with HAM/TSP. Confocal laser scanning microscopy with our unique staining procedure made it possible to visualize HTLV-1-specific CTLs infiltrating the CNS of the HAM/TSP patients. The frequency of HTLV-1-specific CTLs was more than 20% of CD8-positive cells infiltrating the CNS. In addition, HTLV-1 proteins were detected in CD4-positive infiltrating T lymphocytes but not CNS resident cells. Although neurons were generally preserved, apoptotic oligodendrocytes were frequently in contact with CD8-positive cells; this likely resulted in demyelination. These findings suggest that the immune responses of the CTLs against HTLV-1-infected CD4-positive lymphocytes migrating into the CNS resulted in bystander neural damage.
在人类嗜T淋巴细胞病毒1型（HTLV-1）相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者外周血中，活化的HTLV-1特异性CD8阳性细胞毒性T淋巴细胞（CTL）显著增加，HAM/TSP是一种由HTLV-1引起的中枢神经系统炎性疾病。尽管病毒特异性CTL在清除病毒感染细胞中起关键作用，但HTLV-1特异性CTL在HAM/TSP发病机制中的潜在作用仍不清楚。为解决这一问题，我们评估了3例HAM/TSP患者脊髓中HTLV-1特异性CTL的浸润情况以及HTLV-1蛋白的表达。通过我们独特的染色程序进行共聚焦激光扫描显微镜检查，使得可视化HAM/TSP患者中枢神经系统中浸润的HTLV-1特异性CTL成为可能。HTLV-1特异性CTL的频率超过浸润中枢神经系统的CD8阳性细胞的20%。此外，在浸润的CD4阳性T淋巴细胞中检测到HTLV-1蛋白，但在中枢神经系统驻留细胞中未检测到。尽管神经元通常得以保留，但凋亡的少突胶质细胞经常与CD8阳性细胞接触；这可能导致脱髓鞘。这些发现表明，CTL针对迁移到中枢神经系统的HTLV-1感染的CD4阳性淋巴细胞的免疫反应导致了旁观者神经损伤。
