Pre-TCR signaling and inactivation of p53 induces crucial cell survival pathways in pre-T cells

被引：111
作者：
Haks, MC
Krimpenfort, P
van den Brakel, JHN
Kruisbeek, AM
机构：
[1] Antoni Van Leeuwenhoek Huis, Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands
[2] Antoni Van Leeuwenhoek Huis, Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands
来源：
IMMUNITY | 1999年 / 11卷 / 01期
关键词：
D O I：
10.1016/S1074-7613(00)80084-9
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Signaling through the pre-TCR is essential for early T cell development and is severely impaired in mice lacking the CD3 gamma chain of the pre-TCR. We here address the molecular mechanisms underlying this defect. Impaired pre-TCR signaling is shown to be associated with a profound increase in the number of apoptotic CD4(-)CD8(-) (DN) thymocytes. introduction of p53 deficiency into CD3 gamma-deficient mice completely reverses the cell survival defect in CD3 gamma-deficient DN thymocytes and rescues the block in pre-T cell differentiation. In addition, the CD4(+)CD8(+) (DP) compartment is expanded to its normal size. These findings suggest that the pre-TCR regulates progression through the DNA-damage checkpoint of the DN to DP transition by inactivating p53.
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收藏
页码：91 / 101
页数：11
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