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The lck Promoter-Driven Expression of the Wilms Tumor Gene WT1 Blocks Intrathymic Differentiation of T-Lineage Cells

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Abstract

In the thymi of WT1-transgenic (Tg) mice with the 17AA+/KTS- spliced form of the Wilms tumor gene WT1 driven by the lck promoter, the frequencies of CD4-CD8- double-negative (DN) thymocytes were significantly increased relative to those in normal littermates. Of the 4 subsets of CD4-CD8- DN thymocytes, the DN1 (CD44+CD25-) subset increased in both frequency and absolute cell number, whereas the DN2 (CD44+CD25+) and DN3 (CD44-CD25+) subsets decreased, indicating the blocking of thymocyte differentiation from the DN1 to the DN2 subsets. Furthermore, CD4-CD8+ T-cell receptor (TCR) γδ T-cells increased in both frequency and absolute cell number in the spleen and peripheral blood of the WT1-Tg mice relative to those of normal littermates. The CD8 molecules of these CD4-CD8+ TCR78 T-cells were CD8aß, suggesting that they originated from the thymus. These results are the first direct evidence demonstrating that the WT1 gene is involved in the development and differentiation of T-lineage cells.IntJHematol. 2003;77:463-470.

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Authors and Affiliations

  1. Departments of Clinical Laboratory Science, Japan

    Hanfen Li, Kotomi Kawasaki, Yukiko Kishimoto, Hiroko Nakajima, Keisuke Kanato, Yusuke Oji & Haruo Sugiyama

  2. Molecular Medicine, Osaka University Medical School, Osaka, Japan

    Yoshihiro Oka, Akihiro Tsuboi, Momotaro Asada, Sumiyuki Nishida, Tomoki Masuda, Masaki Murakami, Naoki Hosen, Manabu Kawakami, Hiroyasu Ogawa & Ichiro Kawase

  3. Department of Medicine, Osaka Minami National Hospital, Osaka, Japan

    Tamotsu Yamagami

  4. The University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Toru Miyazaki

  5. Fox-Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Sei-ichi Yusa

  6. Department of Cell Biology, Basel University, Basel, Switzerland

    Fritz Melchers

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Li, H., Oka, Y., Tsuboi, A. et al. The lck Promoter-Driven Expression of the Wilms Tumor Gene WT1 Blocks Intrathymic Differentiation of T-Lineage Cells. Int J Hematol 77, 463–470 (2003). https://doi.org/10.1007/BF02986614

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