Generation and Differentiation of IL-17-Producing CD4+ T Cells in Malignant Pleural Effusion
Generation and Differentiation of IL-17-Producing CD4+ T Cells in Malignant Pleural Effusion
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DOI：
10.4049/jimmunol.1001728
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发表时间：
2010-11-15
影响因子：
4.4
通讯作者：
Shi, Huan-Zhong
中科院分区：
文献类型：
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作者：
Ye, Zhi-Jian;Zhou, Qiong;Shi, Huan-Zhong
在一些人类癌症中发现产生il -17的CD4(+) T （Th17）细胞增加；然而，Th17细胞在调节恶性胸腔积液（MPE）抗肿瘤反应中的可能作用仍有待阐明。本研究采用流式细胞术或双免疫荧光染色检测肺癌患者MPE和外周血中Th17细胞的分布和表型特征。探讨细胞因子对Th17细胞产生和分化的影响。体外观察趋化因子CCL20和CCL22对Th17细胞的趋化活性。结果发现MPE中Th17细胞较血液中增加。体外实验表明，IL-1 β、IL-6、IL-23或它们的不同组合可促进Th17细胞从初始CD4(+) T细胞生成和分化。MPE对Th17细胞具有趋化作用，这种活性被抗ccl20和/或CCL22抗体部分阻断。我们的数据还表明，MPE中Th17细胞的积累预示着患者生存率的提高。由此可见，MPE中Th17细胞的过度表达可能是由于胸膜促炎细胞因子刺激Th17细胞分化和扩增以及胸膜趋化因子CCL20和CCL22诱导Th17细胞从外周血中募集所致。此外，MPE中Th17细胞的积累预示着患者生存率的提高。这些数据为开发基于清除癌症患者的这种细胞群的免疫增强策略提供了基础。免疫学杂志，2010,18(5):648 - 654。
IL-17-producing CD4(+) T (Th17) cells have been found to be increased in some human cancers; however, the possible implication of Th17 cells in regulating antitumor responses in malignant pleural effusion (MPE) remains to be elucidated. In the current study, distribution and phenotypic features of Th17 cells in both MPE and peripheral blood from patients with lung cancer were determined by flow cytometry or double immunofluorescence staining. The impacts of cytokines on Th17 cell generation and differentiation were explored. The chemoattractant activity of chemokines CCL20 and CCL22 for Th17 cells in vitro was also observed. It was found that the increased Th17 cells could be found in MPE compared with blood. The in vitro experiments showed that IL-1 beta, IL-6, IL-23, or their various combinations could promote Th17 cell generation and differentiation from naive CD4(+) T cells. MPE was chemotactic for Th17 cells, and this activity was partly blocked by anti-CCL20 and/or CCL22 Abs. Our data also showed that the accumulation of Th17 cells in MPE predicted improved patient survival. It could be concluded that the overrepresentation of Th17 cells in MPE might be due to Th17 cell differentiation and expansion stimulated by pleural pro-inflammatory cytokines and to recruitment of Th17 cells from peripheral blood induced by pleural chemokines CCL20 and CCL22. Furthermore, the accumulation of Th17 cells in MPE predicted improved patient survival. These data provide the basis for developing immune-boosting strategies based on ridding the cancer patient of this cell population. The Journal of Immunology, 2010, 185: 6348-6354.