Izumo Shuji
Division of Molecular Pathology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University.
Rinsho Shinkeigaku. 2005 Nov;45(11):815-7.
Our series of neuropathologic studies on HAM/TSP and AIDS dementia were reviewed. Studies on HAM/ TSP demonstrated chronic inflammatory process in the spinal cord, accentuated inflammation in the area with slow blood flow in the spinal cord, characteristic adhesion molecule expression for T-cell migration, apoptosis of helper T-cells in active inflammatory lesion, correlation of HTLV-I provirus amount with disease activity, and HTLV-I infection and expression of HTLV-I gene on infiltrated T-cells in the spinal cord lesion. Based on these findings, we have proposed a by-stander mechanism as a pathogenesis of HAM/TSP. HIV-1 also involves the CNS, however, its pathogenesis has not been fully studied yet. To understand the pathogenesis of AIDS dementia, we used a SIV-macaque model and demonstrated that there are two independent pathogenic processes in AIDS dementia; AIDS-dependent neuropil degeneration in the cortex caused by T-cell tropic virus, and immune response against invading virus-infected cells in the white matter caused by macrophage tropic virus. The latter mechanism is similar to that of HAM/TSP. Invasion of virus-infected blood cells inside the CNS and a gradual damage of surrounding CNS tissues caused by prolonged immune attack to these virus-infected cells may be a common pathogenic process of retrovirus induced CNS diseases.
我们回顾了一系列关于热带痉挛性截瘫（HAM/TSP）和艾滋病痴呆症的神经病理学研究。对HAM/TSP的研究表明，脊髓存在慢性炎症过程，脊髓血流缓慢区域炎症加剧，有T细胞迁移的特征性黏附分子表达，活跃炎症病灶中辅助性T细胞凋亡，HTLV-I前病毒量与疾病活动的相关性，以及脊髓病变中浸润T细胞上的HTLV-I感染和HTLV-I基因表达。基于这些发现，我们提出了旁观者机制作为HAM/TSP的发病机制。HIV-1也累及中枢神经系统，但其发病机制尚未得到充分研究。为了解艾滋病痴呆症的发病机制，我们使用了猴免疫缺陷病毒（SIV）猕猴模型，并证明艾滋病痴呆症存在两个独立的致病过程；嗜T细胞病毒引起的皮质区艾滋病相关神经纤维变性，以及嗜巨噬细胞病毒引起的白质中针对入侵病毒感染细胞的免疫反应。后一种机制与HAM/TSP相似。中枢神经系统内病毒感染血细胞的侵入以及对这些病毒感染细胞的长期免疫攻击导致周围中枢神经系统组织的逐渐损伤，可能是逆转录病毒诱导的中枢神经系统疾病的共同致病过程。
