ミウラ　ミチ   Michi Miura   三浦　未知    所属   川崎医科大学  医学部 基礎医学　微生物学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Protective effect of cytotoxic T lymphocytes targeting HTLV-1 bZIP factor.
掲載誌名	正式名：Blood 略　 称：Blood ISSNコード：15280020/00064971
掲載区分	国外
巻・号・頁	126(9),pp.1095-105
著者・共著者	Sugata Kenji, Yasunaga Jun-Ichirou, Mitobe Yuichi, Miura Michi, Miyazato Paola, Kohara Michinori, Matsuoka Masao
発行年月	2015/08
概要	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.
DOI	10.1182/blood-2015-04-641118
PMID	26063164