胸腺肽α1对慢性乙型肝炎患者外周血树突状细胞调节作用的体外研究

背景：近年研究显示慢性乙型肝炎（CHB）患者体内树突状细胞（DC）存在不同程度的功能缺失。胸腺肽α1（T-α1）是一种生物学应答调节物质,对CHB的临床治疗有较好疗效。目的：研究T-α1对CHB患者外周血DC分化和功能成熟的影响,寻求改善DC功能的途径。方法：从12例CHB患者和10名健康志愿者的外周血单个核细胞（PBMC）中分离培养DC。培养过程中应用不同浓度T-α1干预DC。以流式细胞仪检测DC表面标志,以甲基噻唑基四唑（MTT）实验检测混合淋巴细胞反应中DC刺激T细胞增殖的能力。结果：从PBMC分离培养得到的外周血DC呈现典型树突状形态。CHB组DC表面标记物CD80、CD86、人白细胞位点DR抗原（HLA-DR）水平以及刺激T细胞增殖的能力显著低于正常对照组（P〈0.001）;经T-α1干预后,两组上述指标均较相应空白对照升高,尤以0.5μg/mlT-α1的作用为著（P〈0.05）,可使CHB组上述指标恢复至正常水平。结论：T-α1能促进CHB患者外周血DC分化和功能成熟,在CHBDC疫苗的研究中可能具有重要价值。

In vitro Modulating Effect of Thymosin α1 OR Peripheral Blood-derived Dendritic Cells in Patients with Chronic Hepatitis B

Background： Recently,some studies demonstrated that loss of function of dendritic cells （DC） might be observed in patients with chronic hepatitis B （CHB）. Thymosin α1 （T-α1） is a biological response modifier,which has been used clinically and effectively in the treatment of CHB. Aims： To investigate the effect of T-α1 on differentiation and functional maturation of peripheral blood-derived DC in CHB patients,and to explore the potential of this approach for improving DC function. Methods： DC was isolated in vitro by culturing the peripheral blood mononuclear cells （PBMC） from 12 CHB patients and 10 healthy volunteers. T-α1 at different levels was used in the interventional study of DC. Surface markers of DC were detected by flow cytometry,and the stimulatory capacity of DC on T-cell proliferation was determined in mixed lymphocyte reaction by methyl thiazolyl tetrazolium （MTT） assay. Results： Cells isolated from cultured PBMC presented typical morphological features of DC. The expressions of DC surface markers CD80,CD86 and human leukocyte antigen locus DR （HLA-DR） in CHB patients were much lower than those in normal controls and the stimulatory capacity of DC on T-cell proliferation in CHB patients decreased significantly （P〈0.001）. In both CHB patients and normal controls,T-α1,especially at the level of 0.5 μg/ml,could increase all the indexes mentioned above （P〈0.05）. When treated with 0.5 μg/ml T-α1,the expressions of DC surface markers and its stimulatory capacity recovered to normal values. Conclusions： T-α1 can promote the differentiation and functional maturation of peripheral blood-derived DC in CHB patients,and may be valuable in the development of DC vaccine for CHB.