Kohu Kazuyoshi, Sato Takehito, Ohno Shin-Ichiro, Hayashi Keitaro, Uchino Ryuji, Abe Natsumi, Nakazato Megumi, Yoshida Naomi, Kikuchi Toshiaki, Iwakura Yoichiro, Inoue Yoshihiro, Watanabe Toshio, Habu Sonoko, Satake Masanobu
Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
J Immunol. 2005 Mar 1;174(5):2627-36. doi: 10.4049/jimmunol.174.5.2627.
The Runx family of transcription factors is thought to regulate the differentiation of thymocytes. Runx3 protein is detected mainly in the CD4(-)8(+) subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly implicates Runx3 in CD4 silencing, but does not necessarily prove its role in the differentiation of CD4(-)8(+) thymocytes per se. In the present study, we created transgenic mice that overexpress Runx3 and analyzed the development of thymocytes in these animals. In the Runx3-transgenic thymus, the number of CD4(-)8(+) cells was greatly increased, whereas the numbers of CD4(+)8(+) and CD4(+)8(-) cells were reduced. The CD4(-)8(+) transgenic thymocytes contained mature cells with a TCR(high)HSA(low) phenotype. These cells were released from the thymus and contributed to the elevated level of CD4(-)8(+) cells relative to CD4(+)8(-) cells in the spleen. Runx3 overexpression also increased the number of mature CD4(-)8(+) thymocytes in mice with class II-restricted, transgenic TCR and in mice with a class I-deficient background, both of which are favorable for CD4(+)8(-) lineage selection. Thus, Runx3 can drive thymocytes to select the CD4(-)8(+) lineage. This activity is likely to be due to more than a simple silencing of CD4 gene expression.
转录因子Runx家族被认为可调节胸腺细胞的分化。Runx3蛋白主要在T淋巴细胞的CD4(-)8(+)亚群中检测到。在Runx3缺陷小鼠的胸腺中，CD4表达去抑制，CD4(-)8(+)胸腺细胞无法发育。这清楚地表明Runx3参与CD4沉默，但不一定证明其本身在CD4(-)8(+)胸腺细胞分化中的作用。在本研究中，我们创建了过表达Runx3的转基因小鼠，并分析了这些动物胸腺细胞的发育情况。在Runx3转基因胸腺中，CD4(-)8(+)细胞数量大幅增加，而CD4(+)8(+)和CD4(+)8(-)细胞数量减少。CD4(-)8(+)转基因胸腺细胞包含具有TCR(高)HSA(低)表型的成熟细胞。这些细胞从胸腺释放出来，导致脾脏中CD4(-)8(+)细胞相对于CD4(+)8(-)细胞的水平升高。Runx3过表达还增加了具有II类限制性转基因TCR的小鼠和具有I类缺陷背景的小鼠中成熟CD4(-)8(+)胸腺细胞的数量，这两种情况都有利于CD4(+)8(-)谱系选择。因此，Runx3可驱动胸腺细胞选择CD4(-)8(+)谱系。这种活性可能不仅仅是由于CD4基因表达的简单沉默。
