Tim-1 signaling substitutes for conventional signal 1 and requires costimulation to induce T cell proliferation.
Tim-1 signaling substitutes for conventional signal 1 and requires costimulation to induce T cell proliferation.
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DOI：
10.4049/jimmunol.182.3.1379
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发表时间：
2009-02-01
期刊：
影响因子：
--
通讯作者：
Strom TB
中科院分区：
文献类型：
--
作者：
Mariat C;Degauque N;Balasubramanian S;Kenny J;DeKruyff RH;Umetsu DT;Kuchroo V;Zheng XX;Strom TB
Ag激活的初始T细胞的分化和克隆扩增在适应性免疫应答中起关键作用。T细胞IG粘蛋白（Tim）影响T细胞的活化和分化。Tim-3和Tim-2分别明显调节Th 1和Th 2应答，但Tim-1对T细胞活化的精确影响仍有待确定。我们现在表明，尽管缺乏常规的TCR依赖性信号，但Tim-1在体内和体外的刺激诱导T细胞的多克隆活化1。在该模型中，Tim-1诱导的增殖依赖于成熟树突状细胞提供的强信号2共刺激。在CD 4 + T细胞上的Tim-1与激动剂抗Tim-1 mAb的连接导致游离胞质钙、钙调神经磷酸酶依赖性NF-AT核转位和IL-2转录的升高。由于Tim-4，Tim-1配体，是由成熟的树突状细胞表达，我们提出，Tim-1+ T细胞和Tim-4+树突状细胞之间的相互作用可能会确保最佳的刺激T细胞，当TCR衍生的信号起源于发炎的环境是弱或减弱。
Differentiation and clonal expansion of Ag-activated naive T cells play a pivotal role in the adaptive immune response. T cell Ig mucin (Tim) proteins influence the activation and differentiation of T cells. Tim-3 and Tim-2 clearly regulate Th1 and Th2 responses, respectively, but the precise influence of Tim-1 on T cell activation remains to be determined. We now show that Tim-1 stimulation in vivo and in vitro induces polyclonal activation of T cells despite absence of a conventional TCR-dependent signal 1. In this model, Tim-1-induced proliferation is dependent on strong signal 2 costimulation provided by mature dendritic cells. Ligation of Tim-1 upon CD4+ T cells with an agonist anti-Tim-1 mAb elicits a rise in free cytosolic calcium, calcineurin-dependent nuclear translocation of NF-AT, and transcription of IL-2. Because Tim-4, the Tim-1 ligand, is expressed by mature dendritic cells, we propose that interaction between Tim-1+ T cells and Tim-4+ dendritic cells might ensure optimal stimulation of T cells, when TCR-derived signals originating within an inflamed environment are weak or waning.
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影响因子：
4.4
作者：
Wilker, Peter R.;Sedy, John R.;Murphy, Kenneth M.
通讯作者：
Murphy, Kenneth M.
DOI：
10.1084/jem.20021024
发表时间：
2003-04-21
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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DOI：
10.1084/jem.20062498
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
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Kuchroo VK
DOI：
10.1084/jem.190.10.1517
发表时间：
1999-11-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Singer A
影响因子：
32.4
作者：
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通讯作者：
Casasnovas JM