Human T-Lymphotropic Virus Type I-Associated Myelopathy

Abstract

Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) is a chronic progressive myelopathy that is characterized by spastic paraparesis with bladder dysfunction that is derived from bilateral pyramidal tract involvement and neurogenic bladder, respectively. The primary neuropathological feature of HAM is chronic inflammation in the spinal cord, mainly the lower thoracic cord, which is characterized by perivascular cuffing and parenchymal infiltration of mononuclear cells. Although it is still unclear why only a very small proportion of HTLV-I carriers develop HAM, the key player in the pathogenesis of HAM is the increase of activated HTLV-I-infected cells in the peripheral blood. The exact cellular and molecular events underlying the induction of chronic inflammation in the spinal cord by HTLV-I are still unclear. However, 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, with the cooperation of the positive feedback loop of inflammation that is derived from the migrated HTLV-I-infected cells is probably critical in the immunopathogenesis of HAM. In this review, recent advances in several fields toward the elucidation of the pathomechanisms concomitant with the establishment of new therapeutic strategies in HAM will be discussed along with an overview of the clinical features.