Upregulated TCR zeta Enhances Interleukin-2 Production in T-Cells from Patients with CML

作者：Zha, Xianfeng; Chen, Shaohua; Yang, Lijian; Shi, Li; Li, Bo; Wu, Xiuli; Lu, Yuhong; Li, Yangqiu^*

来源：DNA and Cell Biology, 2012, 31(11): 1628-1635.

DOI：10.1089/dna.2012.1798

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.

• 出版日期2012-11
• 单位暨南大学