Comparison of T cell receptor-induced proximal signaling and downstream functions in immortalized and primary T cells.
Comparison of T cell receptor-induced proximal signaling and downstream functions in immortalized and primary T cells.
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DOI：
10.1371/journal.pone.0005430
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Houtman JC
中科院分区：
文献类型：
--
作者：
Bartelt RR;Cruz-Orcutt N;Collins M;Houtman JC
人类T细胞在病原体清除中起着重要作用，但它们的异常激活也与许多疾病有关。T细胞通过T细胞受体（TCR）和一种或多种共刺激受体的同时诱导而活化。由TCR和/或共刺激受体活化诱导的信号传导途径的表征是至关重要的，因为这些途径是用于人类疾病的新疗法的极好靶点。尽管使用人T细胞系的研究已经提供了对这些信号传导途径的实质性了解，但是还没有进行这些细胞系与活化的外周血T细胞（APBT）的全面、直接的比较来验证它们作为原代T细胞模型的有用性。我们使用定量生物化学技术来比较两种广泛使用的人T细胞系Jurkat E6.1和HuT 78 T细胞对APBT的活化。我们发现HuT 78细胞在近端TCR介导的信号传导事件中与APBT相似。相比之下，Jurkat E6.1细胞具有显著增加的Pyk 2、PLCγ1、Vav 1和Erk 1/Erk 2的位点特异性磷酸化，并且与HuT 78细胞和APBT相比，具有显著更多的Ca 2+通量。在某种程度上，这些作用似乎是由于与HuT 78细胞和APBT相比，Jurkat E6.1细胞中Itk的过表达。两种细胞系在共刺激受体的表达和功能以及在TCR和共刺激受体活化后释放的细胞因子和趋化因子的范围方面不同于APBT。Jurkat E6.1和HuT 78 T细胞与APBT相比具有明显的相似性和差异性。这两种细胞系都有优点和缺点，在选择它们作为模型T细胞系时必须考虑到这一点。
Human T cells play an important role in pathogen clearance, but their aberrant activation is also linked to numerous diseases. T cells are activated by the concurrent induction of the T cell receptor (TCR) and one or more costimulatory receptors. The characterization of signaling pathways induced by TCR and/or costimulatory receptor activation is critical, since these pathways are excellent targets for novel therapies for human disease. Although studies using human T cell lines have provided substantial insight into these signaling pathways, no comprehensive, direct comparison of these cell lines to activated peripheral blood T cells (APBTs) has been performed to validate their usefulness as a model of primary T cells. We used quantitative biochemical techniques to compare the activation of two widely used human T cell lines, Jurkat E6.1 and HuT78 T cells, to APBTs. We found that HuT78 cells were similar to APBTs in proximal TCR-mediated signaling events. In contrast, Jurkat E6.1 cells had significantly increased site-specific phosphorylation of Pyk2, PLCγ1, Vav1, and Erk1/Erk2 and substantially more Ca2+ flux compared to HuT78 cells and APBTs. In part, these effects appear to be due to an overexpression of Itk in Jurkat E6.1 cells compared to HuT78 cells and APBTs. Both cell lines differ from APBTs in the expression and function of costimulatory receptors and in the range of cytokines and chemokines released upon TCR and costimulatory receptor activation. Both Jurkat E6.1 and HuT78 T cells had distinct similarities and differences compared to APBTs. Both cell lines have advantages and disadvantages, which must be taken into account when choosing them as a model T cell line.
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影响因子：
4.4
作者：
Houtman, JCD;Houghtling, RA;Samelson, LE
通讯作者：
Samelson, LE
影响因子：
3.6
作者：
Arimura, Yutaka;Vang, Torkel;Mustelin, Tomas
通讯作者：
Mustelin, Tomas
DOI：
10.2174/1568010043483881
发表时间：
2004-03-01
期刊：
Current Drug Targets - Inflammation and Allergy
影响因子：
--
作者：
Monaco, Claudia;Andreakos, Evangelos;Paleolog, Ewa
通讯作者：
Paleolog, Ewa
影响因子：
4.8
作者：
Heyeck, SD;Wilcox, HM;Berg, LJ
通讯作者：
Berg, LJ
影响因子：
3.3
作者：
Bisset, LR;Schmid-Grendelmeier, P
通讯作者：
Schmid-Grendelmeier, P