title: Pathological mechanisms of human T-cell lymphotropic virus type I-associated myelopathy (HAM/TSP).
abstract: The recent studies have greatly improved our understanding of the pathological mechanisms of human T cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The pathological mechanisms of HAM/TSP based on the histopathological, immunological, and molecular analysis with emphasis on the longitudinal alterations of the disease will be discussed. Immunohistological examination revealed the existence and the activation both of HTLV-I-infected CD4+ cells and HTLV-I-specific CD8+ cytotoxic T lymphocytes in the spinal cord lesions, which suggest that they play an important role in the pathogenesis. Increased expression of several cytokines, Fas/Fas ligand, adhesion molecules, and molecules influencing T cell migration in the lesions have been reported. These cell infiltrates and cytokines they secrete in the lesions may damage bystander neural tissue. Furthermore, longitudinal alterations in the affected spinal cords suggest that the inflammatory process is gradually decreased. Epidemiological studies show that less than 5% of infected individuals develop HAM/TSP and indicate that increased proviral load of HTLV-I is a strong predictor for the development of HAM/TSP. A recent study has shown that the autoantibody for the ribonuclear protein-A1 can cross-react with HTLV-I Tax protein and inhibit neuronal firing ex vivo, indicating that a molecular mimicry of the humoral immune response may be involved in the pathogenesis of HAM/TSP. Based on these studies, two hypotheses can be proposed for the pathogenesis of HAM/TSP, where cellular and humoral immune responses both play important roles.
authors.affiliation: Third Department of Internal Medicine, Kagoshima University Faculty of Medicine, Kagoshima, Japan. osame@m2.kufm.kagoshima-u.ac.jp
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Osame
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis; D053222:Fas Ligand Protein; D016356:Gene Products, tax / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D015493:Paraparesis, Tropical Spastic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D012261:Ribonucleoproteins / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology* / Q000821:virology
chemical_list: D001323:Autoantibodies; D015815:Cell Adhesion Molecules; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016356:Gene Products, tax; D008562:Membrane Glycoproteins; D012261:Ribonucleoproteins