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