Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is an inflammatory disease of the spinal cord and clinically characterized by progressive spastic paraparesis, urinary incontinence, and mild sensory disturbance. The interaction between the host immune response and HTLV-1-infected cells regulates the development of HAM/TSP. HTLV-1 preferentially infects CD4⁺ T cells and is maintained by proliferation of the infected T cells. HTLV-1-infected cells rarely express viral antigens in vivo; however, they easily express the antigens after short-term culture. Therefore, such virus-expressing cells may lead to activation and expansion of antigen-specific T cell responses. Infected T cells with HTLV-1 and HTLV-1-specific CD8⁺ cytotoxic T lymphocytes invade the central nervous system and produce various proinflammatory cytokines and chemokines, leading to neuronal damage and degeneration. Therefore, cellular immune responses to HTLV-1 have been considered to play important roles in disease development of HAM/TSP. Recent studies have clarified the viral strategy for persistence in the host through genetic and epigenetic changes by HTLV-1 and host immune responses including T cell function and differentiation. Newly developed animal models could provide the opportunity to uncover the precise pathogenesis and development of clinically effective treatment. Several molecular target drugs are undergoing clinical trials with promising efficacy. In this review, we summarize recent advances in the immunopathogenesis of HAM/TSP and discuss the perspectives of the research on this disease.

人类 T 淋巴细胞病毒 1 型 (HTLV-1) 与成人 T 细胞白血病/淋巴瘤和 HTLV-1 相关脊髓病/热带痉挛性下肢轻瘫 (HAM/TSP) 相关。HAM/TSP 是一种脊髓炎性疾病，临床特征为进行性痉挛性下肢轻瘫、尿失禁和轻度感觉障碍。宿主免疫反应和 HTLV-1 感染细胞之间的相互作用调节 HAM/TSP 的发展。HTLV-1 优先感染 CD4 ⁺T 细胞并通过受感染 T 细胞的增殖维持。HTLV-1 感染的细胞在体内很少表达病毒抗原；然而，它们在短期培养后很容易表达抗原。因此，这种病毒表达细胞可能会导致抗原特异性 T 细胞反应的激活和扩展。用 HTLV-1 和 HTLV-1 特异性 CD8 ⁺感染的 T 细胞细胞毒性T淋巴细胞侵入中枢神经系统并产生各种促炎细胞因子和趋化因子，导致神经元损伤和变性。因此，对 HTLV-1 的细胞免疫反应被认为在 HAM/TSP 的疾病发展中起重要作用。最近的研究阐明了通过 HTLV-1 的遗传和表观遗传变化以及宿主免疫反应（包括 T 细胞功能和分化）在宿主中持续存在的病毒策略。新开发的动物模型可以为揭示临床有效治疗的精确发病机制和发展提供机会。几种分子靶向药物正在进行临床试验，具有良好的疗效。在这次审查中，