Expression of Fas/FasL in CD8+T and CD3+Foxp3+Treg Cells - Relationship with Apoptosis of Circulating CD8+ T Cells in Hepatocellular Carcinoma Patients
Expression of Fas/FasL in CD8+T and CD3+Foxp3+Treg Cells - Relationship with Apoptosis of Circulating CD8+ T Cells in Hepatocellular Carcinoma Patients
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DOI：
10.7314/apjcp.2014.15.6.2613
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Wang, Qiu-Cheng
中科院分区：
文献类型：
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作者：
Guo, Cun-Li;Yang, Xiu-Hua;Wang, Qiu-Cheng
目的：癌症患者的宿主免疫系统功能障碍可能是由于许多因素，包括淋巴细胞凋亡。一些研究表明，Foxp 3（+）T细胞通过表达FasL参与诱导肿瘤患者的这一过程。然而，肝癌患者细胞凋亡与CD 8（+）T细胞和Foxp 3（+）T细胞的关系尚不清楚。本研究旨在探讨肝癌患者CD 8（+）T淋巴细胞和Foxp 3（+）T细胞凋亡水平与Fas/FasL表达的相关性。研究方法：采用流式细胞术检测肝癌患者和正常对照外周血中的CD 8（+）T细胞和CD 3（+）Foxp 3（+）T细胞。评估了CD 8（+）T细胞中凋亡标志物（膜联蛋白V）和死亡受体Fas以及CD 3（+）Foxp 3（+）T细胞中FasL的表达。采用酶联免疫吸附法测定HCC患者血清TGF-β 1水平。观察CD 3（+）Foxp 3（+）T细胞凋亡与Fas、FasL表达的关系。结果如下：HCC患者CD 8（+）T细胞膜联蛋白V结合率和Fas表达率均高于正常对照组，凋亡的CD 8（+）T细胞比例与Fas表达相关。血清TGF-β 1水平与CD 3（+）Foxp 3（+）T细胞呈负相关。结论：Fas/FasL相互作用可能导致HCC患者CD 8 + T细胞过度更新，降低抗肿瘤免疫应答。需要进一步研究Fas（+）CD 8（+）T细胞的体外凋亡诱导。
Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that Foxp3(+)T cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, CD8(+)T cells and Foxp3(+)T cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in CD8(+)T lymphocytes and Foxp3(+)T cells in patients with HCC. Methods: CD8(+)T cells and CD3(+)Foxp3(+)T cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in CD8(+)T cells and FasL in CD3(+)Foxp3(+)T cells were evaluated. Serum TGF-beta 1 levels in patients with HCC were measured by enzyme-linked immunosor bent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in CD3(+)Foxp3(+)T cells was then evaluated. Results: The frequency of CD8(+)T cells binding annexin V and Fas expression in CD8(+)T cells, were all higher in HCC patients than normal controls and the proportion of apoptotic CD8(+)T cells correlated with their Fas expression. Serum TGF-beta 1 levels correlated inversely with CD3(+)Foxp3(+)T cells. Conclusions: Fas/FasL interactions might lead to excessive turnover of CD8(+)T cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in Fas(+)CD8(+)T cells in vitro are required.