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首页> 美国卫生研究院文献>Experimental and Therapeutic Medicine >Effect of TGF-β1 on blood CD4+CD25high regulatory T cell proliferation and Foxp3 expression during non-small cell lung cancer blood metastasis
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Effect of TGF-β1 on blood CD4+CD25high regulatory T cell proliferation and Foxp3 expression during non-small cell lung cancer blood metastasis

机译：TGF-β1对非小细胞肺癌血液转移过程中血液CD4 + CD25高调节性T细胞增殖和Foxp3表达的影响

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Metastatic circulating tumor cells in non-small cell lung cancer (NSCLC) metastasis have been reported to be associated with an immune response. The present study aimed to provide a theoretical basis for the immunomodulatory processes during NSCLC blood metastasis. NSCLC blood and normal peripheral blood mononuclear cells (PBMCs) were collected. The quantity of cluster of differentiation (CD)4+CD25high regulatory T (Treg) cells and the intracellular forkhead box protein 3 (Foxp3) expression in CD4+CD25high Treg cells were determined by flow cytometry. Furthermore, the effect of transforming growth factor β1 (TGF-β1) on NSCLC blood CD4+CD25+ Treg cell proliferation was explored by activating blood mononuclear cells with an anti-CD3 monoclonal antibody, interleukin-2 and different doses of TGF-β1. Reverse transcription-quantitative polymerase chain reaction assays were used to detect the mRNA expression of Foxp3. Carboxyfluorescein succinimidyl ester staining was used to analyze the proliferation dynamics of lymphocyte subsets. Results indicate that the proportion of CD4+ T cells in the blood of patients with NSCLC was significantly higher compared with normal peripheral blood (P<0.01). Foxp3 expression in NSCLC blood Treg cells was significantly decreased compared with normal peripheral blood (P<0.01). NSCLC blood mononuclear cells treated with TGF-β1 at 1, 5 and 25 ng/ml significantly induced Foxp3 expression in CD4+CD25+ Treg cells compared with the control group (P<0.05). The proportion of CD4+CD25+ Treg and CD8+ T cells were elevated in generation 6, 7, 8 after 6 days of TGF-β1 treatment compared with untreated cells. The proportion of CD4+CD25+ Treg and CD8+ T cells were elevated in generation 8, 9 and with TGF-β1 treatment after 8 days compared with untreated cells. These results indicate that CD4+CD25+ Treg cells proliferate at a greater rate compared with CD8+ T cells after 4, 6 or 8 days of treatment. The proportion of CD4+CD25high Treg cells in NSCLC blood was significantly higher (P<0.05) compared with normal peripheral blood. The number of Foxp3+ T cells was significantly lower (P<0.05) compared with normal peripheral blood. The data presented in this study suggest that NSCLC blood CD4+CD25high Treg cells are functionally immature and that TGF-β1 may promote maturation.
机译：据报道，非小细胞肺癌（NSCLC）转移中的转移性循环肿瘤细胞与免疫反应有关。本研究旨在为NSCLC血液转移过程中的免疫调节过程提供理论依据。收集NSCLC血液和正常外周血单个核细胞（PBMC）。 CD4 +中分化分化（CD）4 + CD25 高调节性T细胞（Treg）的数量和细胞内叉头盒蛋白3（Foxp3）的表达流式细胞术检测 CD25 高 Treg细胞。此外，通过用抗CD3激活血液单核细胞，探索了转化生长因子β1（TGF-β1）对NSCLC血液CD4 + CD25 + Treg细胞增殖的影响。单克隆抗体，白介素2和不同剂量的TGF-β1。用逆转录定量聚合酶链反应法检测Foxp3的mRNA表达。羧基荧光素琥珀酰亚胺酯染色用于分析淋巴细胞亚群的增殖动力学。结果表明，NSCLC患者血液中CD4 + T细胞的比例明显高于正常外周血（P <0.01）。与正常外周血相比，NSCLC血液Treg细胞中Foxp3的表达显着降低（P <0.01）。与对照组相比，分别以1、5和25 ng / ml的TGF-β1处理的NSCLC血液单核细胞显着诱导CD4 + CD25 + Treg细胞中Foxp3表达（P <0.05）。 TGF-β1第6、7、8代CD4 + CD25 + Treg和CD8 + T细胞的比例升高处理与未处理的细胞相比。 CD4 + CD25 + Treg和CD8 + T细胞的比例在第8、9代和经过8天的TGF-β1处理后均升高与未处理的细胞相比。这些结果表明，与CD8 + T细胞相比，CD4 + CD25 + Treg细胞在4、6或8天后的增殖速率更高。治疗。与正常人外周血相比，NSCLC血液中CD4 + CD25 高 Treg细胞的比例明显更高（P <0.05）。与正常外周血相比，Foxp3 + T细胞的数量明显减少（P <0.05）。这项研究提供的数据表明，NSCLC血液CD4 + CD25 高 Treg细胞功能不成熟，而TGF-β1可能促进其成熟。

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