T cell-specific loss of Pten leads to defects in central and peripheral tolerance
T cell-specific loss of Pten leads to defects in central and peripheral tolerance
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DOI：
10.1016/s1074-7613(01)00134-0
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发表时间：
2001-05-01
期刊：
影响因子：
32.4
通讯作者：
Mak, TW
中科院分区：
文献类型：
--
作者：
Suzuki, A;Yamaguchi, MT;Mak, TW
PTEN是一种肿瘤抑制基因，在胚胎发生中起重要作用。我们使用Cre-IoxP系统来产生Pten基因的T细胞特异性缺失（Pten（Ml-）小鼠）。所有Pten（Pten-）小鼠在17周时均发生CD 4（+）T细胞淋巴瘤。Pten（β 1-）小鼠显示胸腺细胞结构增加，部分原因是胸腺阴性选择缺陷。Pten（β 1-）小鼠表现出外周B细胞和CD 4（+）T细胞水平升高、CD 4（+）T细胞自发活化、自身抗体产生和高丙种球蛋白血症。Pten（β 1-）T细胞过度增殖，是自身反应性的，分泌增加水平的Th 1/Th 2细胞因子，抵抗凋亡，并显示PKB/Akt和ERK的磷酸化增加。在Pten（β 1-）小鼠中，对SEE的外周耐受性也受损。因此，PTEN是T细胞稳态和自身耐受性的重要调节剂。
PTEN, a tumor suppressor gene, is essential for embryogenesis. We used the Cre-IoxP system to generate a T cell-specific deletion of the Pten gene (Pten(floxl-) mice). All Pten(floxl-) mice develop CD4(+) T cell lymphomas by 17 weeks. Pten(floxl-) mice show increased thymic cellularity due in part to a defect in thymic negative selection. Pten(floxl-) mice exhibit elevated levels of B cells and CD4(+) T cells in the periphery, spontaneous activation of CD4(+) T cells, autoantibody production, and hypergammaglobulinemia. Pten(floxl-) T cells hyperproliferate, are autoreactive, secrete increased levels of Th1/Th2 cytokines, resist apoptosis, and show increased phosphorylation of PKB/Akt and ERK. Peripheral tolerance to SEE is also impaired in Pten(floxl-) mice. PTEN is thus an important regulator of T cell homeostasis and self-tolerance.