Subtle defects in Pre-TCR signaling in the absence of the tec kinase itk
Subtle defects in Pre-TCR signaling in the absence of the tec kinase itk
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DOI：
10.4049/jimmunol.179.11.7561
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发表时间：
2007-12-01
影响因子：
4.4
通讯作者：
Berg, Leslie J.
中科院分区：
文献类型：
--
作者：
Lucas, Julie A.;Felices, Martin;Berg, Leslie J.
alpha beta T cell development in the thymus is dependent on signaling through the TCR. The first of these signals is mediated by the pre-TCR, which is responsible for promoting pre-T cell proliferation and the differentiation of CD4(-)8(-)3(-) (DN) thymocytes into CD4(+)8(+)3(+) (DP) cells. In many cases, T cell signaling proteins known to be essential for TCR signaling in mature T cells are also required for pre-TCR signaling in DN thymocytes. Therefore, it came as a surprise to discover that mice lacking the Tee kinases Itk and RIk, enzymes required for efficient activation of phospholipase C-gamma 1 in mature T cells, showed no obvious defects in pre-TCR-dependent selection events in the thymus. In this report, we demonstrate that DN thymocytes lacking Itk, or Itk and Rik, are impaired in their ability to generate normal numbers of DP thymocytes, especially when placed in direct competition with WT DN thymocytes. We also show that Itk is required for maximal pre-TCR signaling in DN thymocytes. These data demonstrate that the Tee kinases Itk and Rik are involved in, but are not essential for, pre-TCR signaling in the thymus, suggesting that there is an alternative mechanism for activating phospholipase C-gamma 1 in DN thymocytes that is not operating in DP thymocytes and mature T cells.
