p53 prevents maturation of T cell development to the immature CD4-CD8+ stage in Bcl11b-/- mice
p53 prevents maturation of T cell development to the immature CD4-CD8+ stage in Bcl11b-/- mice
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DOI：
10.1016/j.bbrc.2005.01.013
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发表时间：
2005-03-11
影响因子：
3.1
通讯作者：
Kominami, R
中科院分区：
文献类型：
--
作者：
Okazuka, K;Wakabayashi, Y;Kominami, R
信号通路，如前TCR和WNT通路，调节胸腺中的α/βT细胞分化。缺乏TCR前必需成分的小鼠在胸腺细胞发育的(CD4(-)CD8(-))(CD44(-)CD25(+))阶段(DN3)表现出停滞，而将P53缺乏引入这些小鼠可以消除这种停滞，导致过渡到(CD4(+)CD8(+))双阳性(DP)阶段。本文研究了P53失活对Bcl11b(-/-)小鼠胸腺细胞发育的影响，这些小鼠在DN3或(CD4(-)CD8(+))未成熟单阳性(ISP)阶段表现出停滞。在过继转移实验中，来自P53(-/-)Bcl11b(-/-)前体的SCID小鼠的胸腺细胞中未检测到DP胸腺细胞，而来自Bcl11b(-/-)前体的isp胸腺细胞的比例和细胞数量增加了近3倍。细胞的凋亡率一直下降到野生型前体细胞的水平。这些结果表明，在Bcl11b(-/-)小鼠中，P53的失活足以使DN3胸腺细胞分化到胸腺细胞发育的isp阶段，但不足以分化到dp阶段。这为P53介导的一个新的检查点提供了证据，该检查点调控胸腺细胞发育从DN3到ISP期的过渡。(C)2005 Elsevier Inc.保留所有权利。
Signaling pathways such as the pre-TCR and Wnt pathways regulate alpha/beta T cell differentiation in thymus. Mice lacking an essential component of the pre-TCR exhibit arrest at the (CD4(-)CD8(-)) (CD44(-)CD25(+)) stage (DN3) of thymocyte development, and introduction of p53 deficiency into those mice abrogates this arrest, resulting in transition to the (CD4(+)CD8(+)) double-positive (DP) stage. This paper examines the effect of inactivation of p53 on thymocyte development in Bcl11b(-/-) mice that exhibit arrest at the DN3 or (CD4(-)CD8(+)) immature single-positive (ISP) stage. No DP thymocytes were detected in thymocytes of adoptive transfer experiments in scid mice that were derived from p53(-/-)Bcl11b(-/-) precursors but ISP thymocytes increased in the proportion and in the cell number approximately three times higher than those from Bcl11b(-/-) precursors. Consistently, the level of apoptosis decreased to the level of wild-type precursors. These results suggest that inactivation of p53 is sufficient for DN3 thymocytes to differentiate into the ISP, but not to DP, stage of thymocyte development in Bcl11b(-/-) mice. This provides evidence for a novel p53-mediated checkpoint that regulates the transition from the DN3 to ISP stage of thymocyte development. (C) 2005 Elsevier Inc. All rights reserved.