Visualization of HTLV-1–Specific Cytotoxic T Lymphocytes in the Spinal Cords of Patients With HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis

Activated human T-lymphotropic virus type-1 (HTLV-1)-specific CD8-positive cytotoxic T lymphocytes (CTLs) are markedly increased in the periphery of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-1-induced inflammatory disease of the CNS. Although virus-specific CTLs play a pivotal role to eliminate virus-infected cells, the potential role of HTLV-1-specific CTLs in the pathogenesis of HAM/TSP remains unclear. To address this issue, we evaluated the infiltration of HTLV-1-specific CTLs and the expression of HTLV-1 proteins in the spinal cords of 3 patients with HAM/TSP. Confocal laser scanning microscopy with our unique staining procedure made it possible to visualize HTLV-1-specific CTLs infiltrating the CNS of the HAM/TSP patients. The frequency of HTLV-1-specific CTLs was more than 20% of CD8-positive cells infiltrating the CNS. In addition, HTLV-1 proteins were detected in CD4-positive infiltrating T lymphocytes but not CNS resident cells. Although neurons were generally preserved, apoptotic oligodendrocytes were frequently in contact with CD8-positive cells; this likely resulted in demyelination. These findings suggest that the immune responses of the CTLs against HTLV-1-infected CD4-positive lymphocytes migrating into the CNS resulted in bystander neural damage.