Pathogenesis of human T‐lymphotropic virus type 1‐associated myelopathy/tropical spastic paraparesis

Human T‐lymphotropic virus type 1 ( HTLV ‐1) is a human retrovirus that preferentially infects CD 4+ lymphocytes in vivo . The virus causes a hematological malignancy known as adult T‐cell leukemia, and an inflammatory disease in the central nervous system ( CNS ) called HTLV ‐1‐associated myelopathy/tropical spastic paraparesis ( HAM / TSP ). Approximately 0.3% of HTLV ‐1‐infected individuals develop HAM / TSP . HAM / TSP patients show spastic paraparesis and sphincter dysfunction, as well as sensory disturbance of the lower extremities, which corresponds to pathological lesions in the spinal cord. Although the majority of HAM / TSP patients progress slowly, this disease progresses rapidly in some patients. An increased HTLV ‐1 proviral load is more common in HAM / TSP patients than in asymptomatic HTLV ‐1 carriers, and is considered to be a strong risk factor for HAM / TSP development. A prominent cellular immune response in HAM / TSP patients is a significantly elevated number of HTLV ‐1 Tax‐specific CD 8+ cytotoxic T lymphocytes ( CTL ) in peripheral blood mononuclear cells compared with asymptomatic HTLV ‐1 carriers. Additionally, CD 4+ and CD 8+ lymphocytes accumulate in the perivascular areas of spinal cords in HAM / TSP patients. Viral DNA , mRNA and proteins are detected only in infiltrating CD 4+ T cells, but not in neural cells. A high proportion of HTLV ‐1‐specific CTL infiltrates the CNS. Furthermore, some neural cells surrounding the CTL , predominantly oligodendrocytes, undergo apoptosis. These findings suggest the pathogenesis that the HTLV ‐1‐specific inflammation induced by the interaction of HTLV ‐1‐infected CD 4+ T cells and HTLV ‐1‐specific CD 8+ CTL causes bystander damage in the CNS. In the present review, a more exact pathogenesis of HAM / TSP is discussed based on virology, immunology and neuropathology.