title: Reduced Tim-3 expression on human T-lymphotropic virus type I (HTLV-I) Tax-specific cytotoxic T lymphocytes in HTLV-I infection.
abstract: T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) and programmed cell death-1 (PD-1) are T cell exhaustion molecules. We investigated the expression of Tim-3 and PD-1 in human T-lymphotropic virus type I (HTLV-I) infection. Tim-3 expression, but not PD-1 expression, was reduced on CD4(+) and CD8(+) T cells of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and HTLV-I carriers as compared with healthy controls. Tim-3 expression was also reduced in HTLV-I Tax-specific cytotoxic T lymphocytes (CTLs) as compared with cytomegalovirus-specific CTLs. Tim-3(+), but not PD-1(+), Tax-specific CTLs produced less interferon-γ and exhibited low cytolytic activity. However, we observed no difference in the expression of Tim-3 or cytolytic activity between Tax-specific CTLs of HAM/TSP patients or carriers. Moreover, HTLV-I-infected CD4(+) T cells showed decreased Tim-3 expression. These data suggest that Tim-3 expression is reduced in HTLV-I infection and that a high number of Tim-3(-) HTLV-I-specific CTLs preserves their cytolytic activity, thereby controlling viral replication.
authors.affiliation: Division of Molecular Pathology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.
authors.forename: Nashwa H
authors.initials: NH
authors.lastname: Abdelbary
authors.forename: Hazem M
authors.initials: HM
authors.lastname: Abdullah
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hayashi
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
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kubota
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015536:Down-Regulation; D005260:Female; D016356:Gene Products, tax / Q000276:immunology*; D015490:HTLV-I Infections / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology*
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D016356:Gene Products, tax; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C514970:tax protein, Human T-lymphotrophic virus 1