Upregulated TCRζ Enhances Interleukin-2 Production in T-Cells from Patients with CML
Upregulated TCRζ Enhances Interleukin-2 Production in T-Cells from Patients with CML
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DOI：
10.1089/dna.2012.1798
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发表时间：
2012-11-01
影响因子：
3.1
通讯作者：
Li, Yangqiu
中科院分区：
文献类型：
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作者：
Zha, Xianfeng;Chen, Shaohua;Li, Yangqiu
T细胞免疫缺陷是慢性粒细胞白血病（CML）患者的常见特征，在这些患者的T细胞中检测到CD 3水平不足，这可能代表与较低T细胞活化相关的特征。在这项研究中，我们探讨了强制TCR zeta基因表达可能上调T细胞受体（TCR）信号激活和逆转CML患者T细胞中白细胞介素-2（IL-2）产生的可能性。将表达TCR ζ的重组真核载体通过核转染法转染入T细胞。通过Western印迹和酶联免疫吸附测定（ELISA）测量用抗CD 3和抗CD 28抗体活化的TCR ζ转染的CD 3 + T细胞中的磷酸化TCR ζ、磷酸化NF-κ B和IL-2水平。在TCR ζ转染的CD 3 + T细胞中发现TCR ζ水平显著增加。在CD 3和CD 28抗体刺激后，证明了显著更高的磷酸化TCR ζ链水平，并且TCR ζ上调的T细胞中IL-2产生的增加与磷酸化NF-κ B的表达增加相关。结论：TCRzeta基因转染可修复CML患者T细胞TCRzeta链缺陷，并提高T细胞IL-2的产生。白血病特异性克隆扩增的T细胞中TCR ζ链重建可能有效地增加其抗白血病细胞毒性的活化。
T-cell immunodeficiency is a common feature in patients with chronic myeloid leukemia (CML), and deficiency in CD3 levels was detected in T cells from these patients, which may represent a characteristic that is related to a lower T cell activation. In this study, we explored the possibility that forced TCR zeta gene expression may upregulate T cell receptor (TCR) signaling activation and reverse interleukin-2 (IL-2) production in T cells from patients with CML. A recombinant eukaryotic vector expressing TCR zeta was transfected into T cells by nucleofection. Phosphorylated TCR zeta, phosphorylated NF-kappa B, and the IL-2 level in TCR zeta-transfected CD3 + T cells that were activated with anti-CD3 and anti-CD28 antibodies were measured by Western blot and enzyme-linked immunosorbent assay (ELISA). Significantly increased TCR zeta levels were found in TCR zeta-transfected CD3 + T cells. After CD3 and CD28 antibody stimulation, a significantly higher phosphorylated TCR zeta chain level was demonstrated, and an increased IL-2 production in TCR zeta-upregulated T cells was associated with the increased expression of the phosphorylated NF-kappa B. In conclusion, TCR zeta gene transfection could restore TCR zeta chain deficiency and enhance IL-2 production in T cells from patients with CML. It is possible that TCR zeta chain reconstitution in leukemia-specific, clonally expanded T cells will effectively increase their activation of antileukemia cytotoxicity.