HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP): the role of HTLV-I-infected Th1 cells in the pathogenesis, and therapeutic strategy

Abstract

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive myelopathy characterized by bilateral pyramidal tract involvement with sphincteric disturbances. The primary neuropathological feature of HAM/TSP is chronic myelitis characterized by perivascular cuffing and parenchymal infiltration of lymphocytes. Although the exact cellular and molecular events underlying the induction of chronic inflammation in the spinal cord by HTLV-I are still unclear, a long-standing bystander mechanism, such as the destruction of surrounding nervous tissue by the interaction between HTLV-I-infected CD4+ T cells and HTLV-I-specific cytotoxic T cells in the spinal cord, is probably critical in the immunopathogenesis of HAM/TSP. In this review, the role of HTLV-I-infected CD4+ T cells as activated Th1 cells in the peripheral blood will be discussed as the first responders of this mechanism in the immunopathogenesis of HAM/TSP. Since the discovery of HAM/TSP, various therapeutic approaches, such as immunomodulatory or anti-viral drugs, have been used for HAM/TSP patients. However, an effective therapeutic strategy against HAM/TSP is still unavailable. As HTLV-I-infected CD4+ T cells are the first responders in the immunopathogenesis of HAM/TSP, the ideal treatment is the elimination of HTLV-I-infected cells from the peripheral blood. In this review, the focus will be on therapeutic strategies aimed at targeting HTLV-I-infected CD4+ T cells in HAM/TSP patients.