Search

To investigate whether the Fas/Fas ligand (FasL) system is involved in the pathogenesis of HTLV-I associated myelopathy (HAM), expression of Fas/FasL in the spinal cord lesions of HAM patients was examined by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Fas was preferentially expressed on infiltrating T cells in active-chronic lesions of HAM. FasL expression was up-regulated on various cells, mainly microglia/macrophages in active-chronic lesions. In contrast, Fas expression was markedly down-regulated in inactive-chronic lesions of HAM patients who had a long duration of illness. The expressions of Fas/FasL in inactive-chronic lesions were comparable to those of normal controls. In normal controls, vascular endothelial cells constitutively displayed both Fas and FasL immunoreactivity, while microglia expressed FasL. RT-PCR confirmed constitutive expression of both Fas mRNA and FasL mRNA in the spinal cords of HAM patients, and in controls. Our results indicate that Fas/FasL system is involved in the inflammatory process in the central nervous system of HAM patients. [ABSTRACT FROM AUTHOR]

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the spinal cord in which HTLV-I Tax-specific cytotoxic T lymphocytes (CTL) have been suggested to be immunopathogenic. However, it is unknown whether the HTLV-I-specific CTL in the central nervous system differ from those in the periphery. We investigated functional T-cell receptor diversity in HTLV-I Tax11-19-specific CTL clones derived from peripheral blood and cerebrospinal fluid (CSF) of a HAM/TSP patient using analogue peptides of the viral antigen. CTL responses to the analogue peptides varied between T-cell clones, however, CTL clones from CSF showed limited recognition of the peptides when compared to those from peripheral blood. This suggests that CTL with highly focused specificity for HTLV-I Tax accumulate in the CSF and may contribute to the pathogenesis of HAM/TSP.Furthermore, this study provides a rationale for analogue peptide-based immunotherapeutic strategies focusing on the immunopathogenic T-cells in HTLV-I-associated neurologic disease. [ABSTRACT FROM AUTHOR]

Human T-lymphotropic virus type 1 (HTLV-I) is a pathogenic retrovirus associated with a chronic progressive myelopathy, termed HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), as well as adult T-cell leukemia (ATL). A chronic inflammatory process has been implicated in HAM/TSP by a pathological study, but the exact mechanism still remains unknown. To understand better the complex mechanism of disease induction by HTLV-I, I studied the spreading pattern of HTLV-I in both peripheral blood mononuclear cells (PBMNCs) and central nervous system (CNS) tissues in patients with HAM/TSP using a quantitative polymerase chain reaction (PCR) method. My results indicated the primary event to be the efficient replication of HTLV-I in vivo, whereas HTLV-I is likely to be present in the constituent cells of the CNS in addition to the infiltrating mononuclear cells. [ABSTRACT FROM AUTHOR]