Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.

Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.
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DOI:
10.1371/journal.pone.0000935
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发表时间:
2007-09-26
期刊:
影响因子:
3.7
通讯作者:
Baumgrass R
Baumgrass R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Podtschaske M;Benary U;Zwinger S;Höfer T;Radbruch A;Baumgrass R

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白细胞介素2(IL-2)的表达是辅助性T细胞(Th)活化的关键事件,控制效应Th细胞的扩增和分化,以及调节性T细胞的激活。我们证明,TCR刺激的强度转化为记忆Th细胞表达IL-2的频率,而不是每个细胞的IL-2量。这种决定细胞内IL-2表达的分子开关位于胞内钙离子水平的下游。在这里,我们发现在单个激活的Th细胞中,NFATC2的激活是数字化的,而NF-κB的激活在分级T细胞受体(TCR)信号之后是分级的。随后,NFATc2以全有或全无的方式进入细胞核,将TCR刺激的强度转化为NFATc2和IL-2转录阳性的核数量。因此,所描述的NFATc2开关调节主动参与免疫反应的Th细胞的数量。
The expression of interleukin-2 (IL-2) is a key event in T helper (Th) lymphocyte activation, controlling both, the expansion and differentiation of effector Th cells as well as the activation of regulatory T cells. We demonstrate that the strength of TCR stimulation is translated into the frequency of memory Th cells expressing IL-2 but not into the amount of IL-2 per cell. This molecular switch decision for IL-2 expression per cell is located downstream of the cytosolic Ca2+ level. Here we show that in a single activated Th cell, NFATc2 activation is digital but NF-κB activation is graded after graded T cell receptor (TCR) signaling. Subsequently, NFATc2 translocates into the nucleus in an all-or-none fashion per cell, transforming the strength of TCR-stimulation into the number of nuclei positive for NFATc2 and IL-2 transcription. Thus, the described NFATc2 switch regulates the number of Th cells actively participating in an immune response.
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