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

Abstract

The main pathological feature of human T-lymphotropic virus type I (HTLV-1)- associated myelopathy/tropical spastic paraparesis (HAWTSP) 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 HAWTSP 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 HAWTSP patients. The relationship between HLA haplotype and the risk of the occurrence of HAWTSP 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 HAWTSP 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 HAWTSP patients is still unknown, we must consider therapeutic approaches in HAM/TSP that eliminate HTLV-I-infected CD4⁺ T lymphocytes.

Key Words:

• cytotoxic T lymphocyte activity
• HLA allele
• HTLV-1-associated myelopathy/tropical spastic paraparesis
• human T-lymphotrophic virus type I proviral load
• T-helper cell type 1