E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis
E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis
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DOI：
10.1128/mcb.21.24.8547-8564.2001
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发表时间：
2001-12-01
影响因子：
5.3
通讯作者：
DeGregori, J
中科院分区：
文献类型：
--
作者：
Zhu, JW;Field, SJ;DeGregori, J
E2F活性是控制G向S相变的关键。我们发现，E2F1和E2F2的联合缺失会对造血细胞的增殖和分化产生深远的影响，并会增加肿瘤的发生和降低淋巴细胞的耐受性。E2F1和E2F2的缺失阻碍了B细胞的分化，缺乏E2F1和E2F2的小鼠骨髓造血祖细胞的细胞周期增加。重要的是，我们发现E2F1和E2F2双敲除T细胞在抗原刺激后更快地进入S时相。此外，缺乏E2F1和E2F2的T细胞对阈值下抗原刺激的反应更为广泛。与这些观察结果一致的是，E2F1/E2F2突变小鼠极易发生肿瘤，一些小鼠表现出自身免疫的迹象。
E2F activity is critical for the control of the G, to S phase transition. We show that the combined loss of E2F1 and E2F2 results in profound effects on hematopoietic cell proliferation and differentiation, as well as increased tumorigenesis and decreased lymphocyte tolerance. The loss of E2F1 and E2F2 impedes B-cell differentiation, and hematopoietic progenitor cells in the bone mar-row of mice lacking E2F1 and E2F2 exhibit increased cell cycling. Importantly, we show that E2F1 and E2F2 double-knockout T cells exhibit more rapid entry into S phase following antigenic stimulation. Furthermore, T cells lacking E2F1 and E2F2 proliferate much more extensively in response to subthreshold antigenic stimulation. Consistent with these observations, E2F1/E2F2 mutant mice are highly predisposed to the development of tumors, and some mice exhibit signs of autoimmunity.