Immunopathogenesis of HTLV-I-associated myelopathy/tropical spastic paraparesis

Abstract

The main pathological feature of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic inflammation of the spinal cord characterized by perivascular cuffing of mononuclear cells accompanied by parenchymal lymphocytic infiltration. Although the exact mechanism of the pathogenesis of HAM/TSP is still obscure, immunological abnormalities arising from a high HTLV-I proviral load in peripheral blood lymphocytes (PBL) play an important role in the pathological process of spinal cord lesions in HAM/TSP patients. The relationship between HLA haplotype and the risk of the occurrence of HAM/TSP will be elucidated by results from studies of HLA allele typing. In addition, recent data indicate that HTLV-I and its expression are localized in infiltrated lymphocytes within the spinal cord lesions of HAM/TSP patients rather than in resident central nervous system (CNS) parenchymal cells. Although a bystander damage of the surrounding CNS tissues, in which CD8+ HTLV-I-specific cytotoxic T lymphocyte (CTL) attack HTLV-I-infected lymphocytes, might be involved in the pathological events of the spinal cords of HAM/ TSP patients as one of the actual pathogenetic mechanisms, heightened transmigrating activity of HTLV-I-infected CD4+ T lymphocytes to the CNS tissues may have a key role in the development of HAM/TSP. Therefore, although the exact mechanism underlying the high HTLV-I proviral load in PBL in HAM/TSP patients is still unknown, we must consider therapeutic approaches in HAM/TSP that eliminate HTLV-I-infected CD4+ T lymphocytes.