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ATL-like overgrowth and clonal expansion of HTLV-1 infected CD25+ CD4+ T- lymphocyte in humanized-NOG mouse model

Humanized mice (huNOG) established by the intra-bone marrow transplantation of NOG-SCID mouse with CD133+ hematopoietic stem cells purified from human cord blood were infected with HTLV-1 in vivo by peritonial injection of γ-ray-irradiated MT-2 cells in 3 to 4 months after transplantation.

While normal differentiation of human T lymphocytes was observed in the spleen of uninfected huNOG mouse, HTLV-1 infection increased the number of CD25+ CD4+ T- lymphocytes and resulted in the splenomegaly within several months. In the late period of infection, where almost all of the blood cells in the mouse were composed of infected human T-lymphocytes, cells with highly lobulated or flower-shaped nuclei appeared in the peripheral blood.

Inverse PCR analysis of provirus integration sites revealed the polyclonal infection in the early phase and the oligoclonal expansion of infected T cells mostly in the population of CD25+ CD4+ T- cells in the late phase. Since substantial amount of anti-Gag antibodies and Tax-specific CTLs were detected in the serum and the spleen of infected mice, respectively, the involvement of immune system against HTLV-1 was suggested in the clonal selection of HTLV-1 infected T-cells in this system.

Thus, the HTLV-1 infected huNOG mouse model should provide a valuable system for the analysis of ATL pathogenesis and the development of treatments against various HTLV-1 associated diseases. Results from the analysis of gene expression in HTLV-1 infected T-cells during the course of infection and the effects of in vivo administration of various anti-tumor or anti-viral drugs on the overgrowth of infected T-cells will be discussed.

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Correspondence to Jun-ichi Fujisawa.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Fujisawa, Ji., Tezuka, K., Xun, R. et al. ATL-like overgrowth and clonal expansion of HTLV-1 infected CD25+ CD4+ T- lymphocyte in humanized-NOG mouse model. Retrovirology 8 (Suppl 1), A13 (2011).

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