タケノウチ　ノリヒロ   TAKENOUCHI NORIHIRO   竹之内　徳博    所属   関西医科大学  微生物学講座    職種   准教授
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	An animal model of adult T-cell leukemia-humanized mice with HTLV-1 specific immunity
掲載誌名	正式名：Blood 略　 称：Blood ISSNコード：00064971/15280020
巻・号・頁	123(3),pp.346-355
著者・共著者	Tezuka K, Xun R, Tei M, Ueno T, Tanaka M, Takenouchi N, Fujisawa JI
発行年月	2014/01
概要	Human T-cell leukemia virus type 1 (HTLV-1) is causally associated with adult T-cell leukemia (ATL), an aggressive T-cell malignancy with a poor prognosis. To elucidate ATL pathogenesis in vivo, a variety of animal models have been established; however, the mechanisms driving this disorder remain poorly understood due to deficiencies in each of these animal models. Here, we report a novel HTLV-1–infected humanized mouse model generated by intra–bone marrow injection of human CD1331 stem cells into NOD/Shi-scid/IL-2Rgc null (NOG) mice (IBMI-huNOG mice). Upon infection, the number of CD41 human T cells in the periphery increased rapidly, and atypical lymphocytes with lobulated nuclei resembling ATL-specific flower cells were observed 4 to 5 months after infection. Proliferation was seen in both CD252 and CD251 CD4 T cells with identical proviral integration sites; however, a limited number of CD251-infected T-cell clones eventually dominated, indicating an association between clonal selection of infected T cells and expression of CD25. Additionally, HTLV-1–specific adaptive immune responses were induced in infected mice and might be involved in the control of HTLV-1–infected cells. Thus, the HTLV-1–i nfected IBMI-huNOG mouse model successfully recapitulated the development of ATL and may serve as an important tool for investigating in vivo mechanisms of ATL leukemogenesis and evaluating anti-ATL drug and vaccine candidates. (Blood. 2014;123(3):346-355)
DOI	10.1182/blood-2013-06-508861
文献番号	24196073