title: Visualization of HTLV-1-specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.
abstract: 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.
authors.affiliation: From the Department of Neurology and Geriatrics (EM, HT) and Center for Chronic Viral Diseases (RK, SI), Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima; and Department of Immunology, University of the Ryukyus, Okinawa (YT), Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kubota
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
authors.forename: Shuji
authors.initials: S
authors.lastname: Izumo
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000473:pathology*; D012191:Retroviridae Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D012191:Retroviridae Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases