Notch signaling augments T cell responsiveness by enhancing CD25 expression
Notch signaling augments T cell responsiveness by enhancing CD25 expression
复制标题
DOI：
10.4049/jimmunol.171.6.2896
复制
发表时间：
2003-09-15
影响因子：
4.4
通讯作者：
Pear, WS
中科院分区：
文献类型：
--
作者：
Adler, SH;Chiffoleau, E;Pear, WS
Notch受体通过高度保守的信号通路影响细胞命运决定。Notch 1是T细胞系定型所必需的;然而，Notch信号传导在外周T细胞应答中的作用尚未明确。Notch基因表达被诱导，并且在特异性肽-Ag刺激后，Notch1在原代CD4（+）T细胞中被激活。Notch活性有助于外周T细胞应答，因为内源性Notch活化的抑制以与IL-2的产生减少和高亲和力IL-2R（CD25）的表达相关的方式降低活化T细胞的增殖。相反，在原代T细胞中强制表达组成型活性Notch1导致CD25的表面表达增加，并使这些细胞对同源Ag和IL-2更敏感，如通过细胞分裂所测量的。这些数据表明Notch信号在CD4（+）T细胞应答中的重要作用，其通过增强涉及IL-2及其高亲和力受体的正反馈回路来起作用。
Notch receptors signal through a highly conserved pathway to influence cell fate decisions. Notch1 is required for T lineage commitment; however, a role for Notch signaling has not been clearly defined for the peripheral T cell response. Notch gene expression is induced, and Notch1 is activated in primary CD4(+) T cells following specific peptide-Ag stimulation. Notch activity contributes to the peripheral T cell response, as inhibition of endogenous Notch activation decreases the proliferation of activated T cells in a manner associated with the diminished production of IL-2 and the expression of the high affinity IL-2R (CD25). Conversely, forced expression of a constitutively active Notch1 in primary T cells results in increased surface expression of CD25, and renders these cells more sensitive to both cognate Ag and IL-2, as measured by cell division. These data suggest an important role for Notch signaling during CD4(+) T cell responses, which operates through augmenting a positive feedback loop involving IL-2 and its high affinity receptor.