title: Reduced frequency, diversity, and function of human T cell leukemia virus type 1-specific CD8+ T cell in adult T cell leukemia patients.
abstract: Human T cell lymphotropic virus type 1 (HTLV-1)-specific CTL are thought to be immune effectors that reduce the risk of adult T cell leukemia (ATL). However, in vivo conditions of anti-HTLV-1 CTL before and after ATL development have yet to be determined. To characterize anti-HTLV-1 CTL in asymptomatic HTLV-1 carriers (AC) and ATL patients, we analyzed the frequency and diversity of HTLV-1-specific CD8+ T cells in PBMC of 35 AC and 32 ATL patients using 16 distinct epitopes of HTLV-1 Tax or Env/HLA tetramers along with intracellular cytolytic effector molecules (IFN-gamma, perforin, and granzyme B). Overall frequency of subjects possessing Tax-specific CD8+ T cells was significantly lower in ATL than AC (53 vs 90%; p = 0.001), whereas the difference in Env-specific CD8+ T cells was not statistically significant. AC possessed Tax11-19/HLA-A*0201-specific tetramer+ cells by 90% and Tax301-309/HLA-A*2402-specific tetramer+ cells by 92%. Some AC recognized more than one epitope. In contrast, ATL recognized only Tax11-19 with HLA-A*0201 and Tax301-309 with HLA-A*2402 at frequencies of 30 and 55%. There were also significant differences in percentage of cells binding Tax11-19/HLA-A*0201 and Tax301-309/HLA-A*2402 tetramers between AC and ATL. Anti-HTLV-1 Tax CD8+ T cells in AC and ATL produced IFN-gamma in response to Tax. In contrast, perforin and granzyme B expression in anti-HTLV-1 CD8+ T cells of ATL was significant lower than that of AC. Frequency of Tax-specific CD8+ T cells in AC was related to proviral load in HLA-A*0201. These results suggest that decreased frequency, diversity, and function of anti-HTLV-1 Tax CD8+ T cell clones may be one of the risks of ATL development.
authors.affiliation: Division of Host Response, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kozako
authors.forename: Naomichi
authors.initials: N
authors.lastname: Arima
authors.forename: Shingo
authors.initials: S
authors.lastname: Toji
authors.forename: Izumi
authors.initials: I
authors.lastname: Masamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Akimoto
authors.forename: Heiichiro
authors.initials: H
authors.lastname: Hamada
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Che
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Kakushi
authors.initials: K
authors.lastname: Matsushita
authors.forename: Masahito
authors.initials: M
authors.lastname: Tokunaga
authors.forename: Koichi
authors.initials: K
authors.lastname: Haraguchi
authors.forename: Kimiharu
authors.initials: K
authors.lastname: Uozumi
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takezaki
authors.forename: Shunro
authors.initials: S
authors.lastname: Sonoda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002999:Clone Cells; D005260:Female; D016356:Gene Products, tax / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D016356:Gene Products, tax; D006680:HLA Antigens; D007371:Interferon-gamma