Nakamura Tatsufumi
Department of Social Work, Faculty of Human and Social Studies, Nagasaki International University, Nagasaki 859-3298, Japan.
Pathogens. 2023 Mar 21;12(3):492. doi: 10.3390/pathogens12030492.
Slowly progressive spastic paraparesis with bladder dysfunction, the main clinical feature of human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), is induced by chronic inflammation in the spinal cord, mainly the lower thoracic cord. A long-standing bystander mechanism, such as the destruction of surrounding tissues by inflammatory cytokines, etc., induced under the interaction between infiltrated HTLV-1-infected CD4 T cells and HTLV-1-specific CD8 cytotoxic T cells, has been considered implicated for the induction of chronic inflammation. As this bystander mechanism is triggered conceivably by the transmigration of HTLV-1-infected CD4 T cells to the spinal cord, heightened transmigrating activity of HTLV-1-infected CD4 T cells to the spinal cord might play a crucial role as the first responder in the development of HAM/TSP. This review evaluated the functions of HTLV-1-infected CD4 T cells in HAM/TSP patients as the prerequisite for the acquisition of the activity such as adhesion molecule expression changes, small GTPases activation, and expression of mediators involved in basement membrane disruption. The findings suggest that HTLV-1-infected CD4 T cells in HAM/TSP patients have enough potential to facilitate transmigration into the tissues. Future HAM/TSP research should clarify the molecular mechanisms leading to the establishment of HTLV-1-infected CD4 T cells as the first responder in HAM/TSP patients. In addition, a regimen with an inhibitory activity against the transmigration of HTLV-1-infected CD4 T cells into the spinal cord might be recommended as one of the therapeutic strategies against HAM/TSP patients.
缓慢进展性痉挛性截瘫伴膀胱功能障碍是人类T细胞白血病病毒1型（HTLV-1）相关脊髓病/热带痉挛性截瘫（HAM/TSP）的主要临床特征，由脊髓慢性炎症引起，主要累及胸段脊髓下部。一种长期存在的旁观者机制，如炎症细胞因子等对周围组织的破坏，在浸润的HTLV-1感染的CD4 T细胞与HTLV-1特异性CD8细胞毒性T细胞相互作用下诱导产生，被认为与慢性炎症的诱导有关。由于这种旁观者机制可能是由HTLV-1感染的CD4 T细胞向脊髓的迁移触发的，HTLV-1感染的CD4 T细胞向脊髓的迁移活性增强可能作为HAM/TSP发病的第一反应者发挥关键作用。本综述评估了HAM/TSP患者中HTLV-1感染的CD4 T细胞的功能，这是获得诸如黏附分子表达变化、小GTP酶激活以及参与基底膜破坏的介质表达等活性的先决条件。研究结果表明，HAM/TSP患者中HTLV-1感染的CD4 T细胞具有促进向组织迁移的足够潜力。未来HAM/TSP的研究应阐明导致HTLV-1感染的CD4 T细胞成为HAM/TSP患者第一反应者的分子机制。此外，作为针对HAM/TSP患者的治疗策略之一，可能推荐一种对HTLV-1感染的CD4 T细胞向脊髓迁移具有抑制活性的治疗方案。
