淋巴细胞趋化因子在慢性阻塞性肺疾病患者外周血中的表达及其对CD4^＋CD8^＋T细胞亚群的影响

Lymphocyte chemokine expression and its effect on peripheral blood CD4^＋ CD8^＋ T-cell subsets in patients with chronic obstructive pulmonary disease

目的 探讨淋巴细胞趋化因子（lymphotactin,XCL1）对COPD患者外周血CD4^＋ T、CD8^＋T细胞亚群及有关炎症因子的影响及机制。方法 随机选取13例COPD 患者（急性加重期和稳定期）和13名健康人,分离外周血T淋巴细胞进行培养,经淋巴细胞趋化因子干预后,用流式细胞仪分别检测外周血中CD4^＋T、CD8^＋ T 细胞亚群变化及其表面Fas、FasL 表达,并用酶联免疫吸附试验（enzymelinkedimmunosorbentassay,ELISA）分别检测血清及细胞培养上清液中的XCL1、IL-2表达水平。结果 AECOPD及稳定期患者外周血中的XCL1的表达均高于健康对照组（P 〈0.05）,AECOPD组又高于稳定期组患者（P 〈0.05）。COPD患者（包括急性发作期与稳定期）T细胞培养液中,XCL1干预组与未干预组相比,XCL1、CD4^＋-Fas、CD4^＋-FasL、CD8^＋-Fas、CD8^＋-FasL 表达增高（P 〈0.05）,CD4^＋/CD8^＋ 降低（P 〈0.05）,而IL-2 表达减少（P 〈0.05）。且XCL1 的表达与CD4^＋-Fas、CD4^＋-FasL、CD8^＋-Fas、CD8^＋-FasL的表达呈正相关,与IL-2的表达及CD4^＋/CD8^＋ 呈负相关。结论 XCL1参与了COPD的炎症过程,其参与炎症反应的机制可能是通过促进Fas、FasL的表达,导致CD4^＋T、CD8^＋ T细胞的凋亡增加,CD4^＋T/CD8^＋T比值下降,造成CD4^＋/CD8^＋ 比例失衡,XCL1还可引起IL-2水平降低,间接导致机体免疫功能紊乱或低下,可能是导致COPD炎症持续存在的重要机制。

Objective In this study, we sought to investigate the relevance of lymphocyte chemokine （lymphotactin, XCL1） expression in patients with chronic obstructive pulmonary disease （COPD） and to analyze the effects of XCL1 expression on CD4^＋ CD8^＋ T-cell subsets and related inflammatory factors. Methods Thirteen patients with COPD [acute exacerbation （AE） and stable phase （SP） ] and 13 healthy individuals were included in the study. Peripheral blood T lymphocytes were isolated and cultured. After XCL1 intervention, subsets of peripheral blood CD4^＋ CD8^＋ T lymphocytes and expression of Fas and FasL were detected by flow cytometry. XCL1 and interleukin （IL）-2 expression in sera and cell culture supernatants were detected by enzyme-linked immunosorbent assay. Results XCL1 expression in the peripheral blood of patients with COPD （both AE and SP） was higher than that in healthy patients. Additionally,XCL1 expression was higher during AE than during SP. Analysis of T cells from the culture medium of COPD patients revealed that CD4^＋ -Fas, CD4^＋ FasL, CD8^＋-Fas, and CD8^＋- FasL subsets increased,while the CD4^＋ CD8^＋ subset decreased following XCL1 intervention. Moreover,IL-2 expression decreased, and XCL1 expression, as well as CD4^＋ Fas, CD4 ^＋ FasL, CD8^＋ Fas, and CD8^＋ -FasL subsets,were positively correlated with IL-2 expression, while the CD4^＋ CD8^＋ subset was negatively correlated. Conclusions XCL1 involved in the inflammatory process of COPD,which through by increasing the expression of Fas, FasL, and resulted in CD4^ ＋ T, CD8 ^＋ T cells apoptosis increased, CD4 ^＋ T/CD8^＋ T decreased, caused the imbalance of the proportion of CD4^＋ /CD8^＋. XCL1 also decreased the level of IL-2,thereby representing an important molecular player in the persistent inflammation observed in COPD.