Phosphoinositide-dependent kinase 1 (PDK1) haplo-insufficiency inhibits production of alpha/beta (α/β) but not gamma delta (γ/δ) T lymphocytes
Phosphoinositide-dependent kinase 1 (PDK1) haplo-insufficiency inhibits production of alpha/beta (α/β) but not gamma delta (γ/δ) T lymphocytes
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DOI：
10.1016/j.febslet.2006.03.022
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发表时间：
2006-04-03
期刊：
影响因子：
3.5
通讯作者：
Cantrell, DA
中科院分区：
文献类型：
--
作者：
Kelly, AP;Hinton, HJ;Cantrell, DA
在本研究中，我们探讨了删除T细胞祖细胞中PDK 1的单个等位基因对α/β和γ/δ T细胞发育的影响。数据显示，删除PDK 1的单个等位基因允许α/β T细胞分化，但阻止它们在胸腺中的增殖扩增。因此，具有PDK 1单倍不足的T细胞的小鼠具有减少的胸腺细胞和α/β外周T细胞的数量。T细胞祖细胞也产生γ/δ T细胞，但与T-PDK 1缺失和单倍体不足小鼠中α/β T细胞的损失相反，γ/δ T细胞的数量增加。WO T细胞的产生依赖于胸腺细胞的增殖性扩增，并由细胞进入细胞周期增殖期的频率和细胞死亡速率之间的平衡决定。在此，我们发现PDK 1单倍不足的胸腺细胞在进入细胞周期的能力方面没有缺陷，但凋亡增加。因此，PDK 1在α/β T淋巴细胞的发育中起决定性作用，但不限制γ/δ T细胞的发育。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
In the present study, we have explored the impact of deleting a single allele of PDK1 in T cell progenitors on alpha/beta and gamma/delta T cell development. The data show that deleting a single allele of PDK1 allows differentiation of alpha/beta T cells but prevents their proliferative expansion in the thymus. Accordingly, mice with T cells that are haplo-insufficient for PDK1 have reduced numbers of thymocytes and alpha/beta peripheral T cells. T cell progenitors also give rise to gamma/delta T cells but in contrast to the loss of alpha/beta T cells in T-PDK1 null and haplo-insufficient mice, there were increased numbers of gamma/delta T cells. The production of WO T cells is dependent on the proliferative expansion of thymocytes and is determined by a balance between the frequency with which cells enter the proliferative phase of the cell cycle and rates of cell death. Herein, we show that PDK1 haplo-insufficient thymocytes have no defects in their ability to enter the cell cycle but show increased apoptosis. PDK1 thus plays a determining role in the development of alpha/beta T lymphocytes but does not limit gamma/delta T cell development. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.