CD4+CD25+ regulatory T lymphocytes in malignant pleural effusion

CD4+CD25+ regulatory T lymphocytes in malignant pleural effusion
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DOI:
10.1164/rccm.200504-588oc
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发表时间:
2005-12-01
影响因子:
24.7
通讯作者:
Wu, C
Wu, C
中科院分区:
医学1区
文献类型:
--
作者:
Chen, YQ;Shi, HZ;Wu, C

文献摘要

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背景:CD4(+)CD25(+)调节性T淋巴细胞的主动抑制在T细胞对外源和自身抗原反应下调中发挥重要作用。目的:分析恶性胸腔积液中CD4(+)CD25(+)调节性T淋巴细胞是否存在并正常发挥作用。方法:检测肺癌恶性胸腔积液和外周血中CD4(+)CD25(+)T淋巴细胞的百分比。采用流式细胞术测定肺癌患者的胸腔积液、胸腔灌洗液和外周血,以及健康对照者的外周血。还检测了叉头转录因子 Foxp3 和细胞毒性淋巴细胞相关抗原 4 的表达。从胸腔积液和外周血中分离CD4(+)CD25(+)和CD4(+)CD25(+)T细胞,进行培养,观察CD4(+)CD25(+)细胞对CD4(+)CD25(-)T细胞体外增殖反应的影响。主要结果:与肺癌患者相比,恶性胸腔积液中CD4(+)CD25(+)T细胞数量增多。来自无胸腔积液的肺癌患者的胸腔灌洗液,这些细胞具有 Foxp3 和细胞毒性淋巴细胞相关抗原 4 的组成型高水平表达。此外,CD4(+)CD25(+) T细胞可有效抑制CD4(+)CD25(-) T细胞的增殖反应,抗细胞毒性淋巴细胞相关抗原4单克隆抗体可降低CD4(+)CD25(+) T细胞的抑制活性。结论:恶性胸腔积液中CD4(+)CD25(+) T细胞表达高水平的Foxp3转录因子,有效抑制CD4(+)CD25(+) T细胞的增殖反应。 CD4+CD25- T 细胞增殖,细胞毒性淋巴细胞相关抗原 4 参与胸膜 CD4(+)CD25(+) T 细胞的抑制活性。
Background: Active suppression by CD4(+)CD25(+) regulatory T lymphocytes plays an important role in the downregulation of T-cell responses to foreign and self-antigens.Objective:To analyze whether the CD4(+)CD25(+) regulatory T lymphocytes exist and function normally in malignant pleural effusion.Methods: The percentages of CD4(+)CD25(+) T lymphocytes in pleural effusion and peripheral blood from patients with lung cancer with malignant effusion, pleural lavage and peripheral blood from patients with lung cancer without effusion, and peripheral blood from healthy control subjects were determined by flow cytometry. The expressions of forkhead transcription factor Foxp3 and cytotoxic lymphocyte-associated antigen-4 were also examined. CD4(+)CD25(+) and CD4(+)CD25(+) T cells from pleural effusion and peripheral blood were isolated, and were cultured to observe the effects of CD4(+)CD25(+) cells on proliferation response of CD4(+)CD25(-) T cells in vitro.Main Results: There were increased numbers of CD4(+)CD25(+) T cells in malignant pleural effusion from patients with lung cancer compared with pleural lavage from patients with lung cancer without pleural effusion, and that these cells have constitutive high-level expression of Foxp3 and cytotoxic lymphocyte-associated antigen-4. Furthermore, CD4(+)CD25(+) T cells mediate potent inhibition of proliferation response of CD4(+)CD25(-) T cells, and anticytotoxic lymphocyte-associated antigen-4 monoclonal antibody could reduce the inhibitory activity of CD4(+)CD25(+) T cells.Conclusions: The increased CD4(+)CD25(+) T cells found in malignant pleural effusion express high levels of Foxp3 transcription factor and potently suppress the proliferation of CD4+CD25- T cells, and cytotoxic lymphocyte-associated antigen-4 is involved in the suppressive activity of pleural CD4(+)CD25(+) T cells.