Visualization of HTLV-1-specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.
Visualization of HTLV-1-specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.
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DOI：
10.1097/nen.0000000000000141
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发表时间：
2015-01
影响因子：
3.2
通讯作者：
Izumo S
中科院分区：
文献类型：
--
作者：
Matsuura E;Kubota R;Tanaka Y;Takashima H;Izumo S
HTLV-1 相关性脊髓病/热带痉挛性截瘫 (HAM/TSP)（一种 HTLV-1 诱发的中枢神经系统炎症性疾病）患者的外周血中，活化的人类 T 淋巴细胞病毒 1 型 (HTLV-1) 特异性 CD8 阳性细胞毒性 T 淋巴细胞 (CTL) 显着增加。尽管病毒特异性 CTL 在消除病毒感染细胞方面发挥着关键作用，但 HTLV-1 特异性 CTL 在 HAM/TSP 发病机制中的潜在作用仍不清楚。为了解决这个问题，我们评估了 3 名 HAM/TSP 患者脊髓中 HTLV-1 特异性 CTL 的浸润和 HTLV-1 蛋白的表达。共聚焦激光扫描显微镜采用我们独特的染色程序，可以观察到浸润 HAM/TSP 患者中枢神经系统的 HTLV-1 特异性 CTL。 HTLV-1 特异性 CTL 的频率超过浸润 CNS 的 CD8 阳性细胞的 20%。此外，在 CD4 阳性浸润 T 淋巴细胞中检测到 HTLV-1 蛋白，但在 CNS 驻留细胞中未检测到。尽管神经元通常被保留，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 CNS 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。
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.