TCR signals mediated by src family kinases are essential for the survival of naive T cells

TCR signals mediated by src family kinases are essential for the survival of naive T cells
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DOI:
10.4049/jimmunol.169.6.2997
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发表时间:
2002-09-15
影响因子:
4.4
通讯作者:
Zamoyska, R
Zamoyska, R
中科院分区:
医学2区
文献类型:
--
作者:
Seddon, B;Zamoyska, R

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识别自身MHC所触发的TCR信号在维持幼稚外周T细胞存活中的作用仍存在争议。在这里,我们研究了Src家族激酶p56(Lck)(Lck)和p59(Fyn)(Fyn)在幼稚T细胞存活中的作用。我们发现,长期生存需要由Src家族激酶传导的信号和通过IL-7R传递的信号的组合。如果没有任何一个信号,幼稚的T细胞会缓慢死亡,但如果两个信号都被移除,细胞损失就会大大加快。在野生型表达水平,TCR信号可以由Fyn或Lck介导,但如果表达为次优水平,则不能单独由Lck介导。在没有Fyn和Lck的情况下,T细胞的消失与TCRzeta链磷酸化的完全丧失和CD5的下调有关,这两者也都是MHC接触依赖性的,表明Src家族激酶在TCR-MHC生存信号的转导中起关键作用。
The role of TCR signals triggered by recognition of self MHCs in maintaining the survival of naive peripheral T cells remains controversial. Here we examine the role of the Src family kinases, p56(lck) (Lck) and p59(fyn) (Fyn), in the survival of naive T cells. We show that long term survival requires a combination of signals transduced by Src family kinases and signals through the IL-7R. In the absence of either one, naive T cells die slowly, but if both signals are removed, cell loss is greatly accelerated. The TCR signal can be mediated by either Fyn or Lck at wild-type levels of expression, but not by Lck alone if expressed suboptimally. The disappearance of T cells in the absence of Fyn and Lck was associated with a complete loss of TCRzeta-chain phosphorylation and down-regulation of CD5, both of which are also MHC contact dependent, indicating that the Src family kinases are critical for transducing a TCR-MHC survival signal.