title: Protective effect of cytotoxic T lymphocytes targeting HTLV-1 bZIP factor.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases in a small percentage of infected individuals. Host immune responses, in particular cytotoxic T lymphocytes (CTLs), influence the proliferation and survival of ATL cells and HTLV-1-infected cells. We generated recombinant vaccinia viruses (rVVs) expressing HTLV-1 basic leucine zipper (bZIP) factor (HBZ) or Tax to study the immunogenic potential of these viral proteins. Vaccination with rVV expressing Tax or HBZ induced specific T-cell responses, although multiple boosters were needed for HBZ. HBZ-stimulated T cells killed HBZ peptide-pulsed T cells and CD4(+) T cells from HBZ transgenic (HBZ-Tg) mice. The anti-lymphoma effect of the CTLs targeting HBZ was tested in mice inoculated with a lymphoma cell line derived from an HBZ-Tg mouse. Transfer of splenocytes from HBZ-immunized mice increased the survival of the lymphoma cell-inoculated mice, suggesting that the anti-HBZ CTLs have a protective effect. The rVV could also induce specific T-cell responses to HBZ and Tax in HTLV-1-infected rhesus monkeys. On the basis of the results of rVV-vaccinated mice and macaques, we identified a candidate peptide (HBZ157-176) for vaccine development. Dendritic cells pulsed with this peptide could generate HBZ-specific CTLs from human CD8(+) T cells. This study demonstrates that HBZ could be a target for immunotherapy of patients with ATL.
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan; Japan Society for the Promotion of Science, Tokyo, Japan; and.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugata
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan;
authors.forename: Jun-Ichirou
authors.initials: J
authors.lastname: Yasunaga
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan;
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mitobe
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan;
authors.forename: Michi
authors.initials: M
authors.lastname: Miura
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan;
authors.forename: Paola
authors.initials: P
authors.lastname: Miyazato
authors.affiliation: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan;
authors.forename: Masao
authors.identifier: http://orcid.org/0000-0002-0473-754X
authors.initials: M
authors.lastname: Matsuoka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D016356:Gene Products, tax / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008253:Macaca mulatta; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016356:Gene Products, tax; D014614:Vaccines, Synthetic; D014764:Viral Proteins