Regulatory T-cell function of adult T-cell leukemia/lymphoma cells

Authors

  • Hiroki Yano,

    1. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan
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    • The authors have no financial conflict of interest.

  • Takashi Ishida,

    Corresponding author
    1. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan
    • Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi 467-8601, Japan
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    • The authors have no financial conflict of interest.

    • Fax: +81-52-852-0849.

  • Atsushi Inagaki,

    1. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan
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    • The authors have no financial conflict of interest.

  • Toshihiko Ishii,

    1. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan
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  • Shigeru Kusumoto,

    1. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan
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  • Hirokazu Komatsu,

    1. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan
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  • Shinsuke Iida,

    1. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan
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  • Atae Utsunomiya,

    1. Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Kagoshima, Japan
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  • Ryuzo Ueda

    1. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan
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Abstract

Adult T-cell leukemia/lymphoma (ATLL) patients are highly immunocompromised, but the underlying mechanism responsible for this state remains obscure. Recent studies demonstrated that FOXP3, which is a master control gene of naturally occurring regulatory T (Treg) cells, is expressed in the tumor cells from a subset of patients with ATLL. Since most ATLL cells express both CD4 and CD25, these tumors might originate from CD4+CD25+FOXP3+ Treg cells, based on their phenotypic characteristics. However, whether ATLL cells actually function as Treg cells has not yet been clearly demonstrated. Here, we show that ATLL cells from a subset of patients are not only hypo-responsive to T-cell receptor-mediated activation, but also suppress the proliferation of autologous CD4+ non-ATLL cells. Furthermore, ATLL cells from this subset of patients secrete only small amounts of IFN-γ, and suppress IFN-γ production by autologous CD4+ non-ATLL cells. These are the first data showing that ATLL cells from a subset of patients function as Treg cells in an autologous setting. The present study provides novel insights into understanding the immunopathogenesis of ATLL, i.e., how HTLV-1-infected cells can survive in the face of host immune responses. It also adds to our understanding of ATLL patients' severely immunocompromised state. © 2007 Wiley-Liss, Inc.

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