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胸腺肽α1对慢性乙型肝炎CD4+CD25+CD127dim/-调节性T淋巴细胞功能的影响
Effect of thymosin α1 on the function of CD4+CD25+CD127dim/- regulatory T cells in chronic hepatitis B patients
文章发布日期:2018年04月04日  来源:  作者:李彧,田颖,杨晓梅,等  点击次数:436次  下载次数:40次

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【摘要】:目的观察胸腺肽α1对慢性乙型肝炎CD4+CD25+CD127dim/-调节性T淋巴细胞(Treg)功能的影响。方法选取2016年12月-2017年7月陕西省人民医院感染性疾病科收治的慢性乙型肝炎患者67例,其中38例接受恩替卡韦抗病毒治疗(对照组),29例接受恩替卡韦联合注射用胸腺肽α1治疗(治疗组),分别于治疗前后分离外周血单个核细胞,流式细胞术检测CD4+CD25+CD127dim/-Treg水平,纯化CD4+CD25+CD127dim/-Treg,与自体CD4+CD25-T淋巴细胞共培养,CCK-8法检测细胞增殖,ELISA法检测细胞因子分泌水平。计量资料2组间比较采用t检验,计数资料组间比较采用χ2检验。结果对照组、治疗组患者经治12周CD4+CD25+CD127dim/- Treg均较基线水平明显下降,差异均有统计学意义(8.85±2.18)% vs (12.32±1.22)%、(9.26±2.30)% vs (13.71±2.32)%,t值分别为4.579、4.803,P值分别为0.0005、0.0003]。选取17例对照组患者和21例治疗组患者检测细胞因子分泌水平。经治12周对照组患者治疗12周后Treg与CD4+CD25-T淋巴细胞共培养系统中细胞增殖和分泌细胞因子水平均无明显变化;治疗组共培养系统中细胞计数较基线水平明显升高,差异有统计学意义[(3.66±0.95)×106个vs (2.07±0.51)×106个,t=5.709,P<0.0001];治疗组共培养细胞分泌抑制性细胞因子IL-10、IL-35水平明显降低,差异均有统计学意义[(41.40±11.89) pg/ml vs (56.53±27.85) pg/ml、(122.9±9.98) pg/ml vs (130.0±15.98) pg/ml,t值分别为2.639、2.459,P值分别为0.019、0.028)],分泌抗病毒细胞因子IFNα、IFNγ水平明显升高,差异均有统计学意义[(297.5±83.56) pg/ml vs (235.6±67.72) pg/ml、(5.83±0.85) pg/ml vs (4.39±0.95) pg/ml,t值分别为2.603、4.659,P值分别0.017、0.0004]。结论胸腺肽α1能够抑制慢性乙型肝炎CD4+CD25+CD127dim/- Treg水平及免疫抑制功能,提高患者免疫功能。
【Abstract】:ObjectiveTo investigate the effect of thymosin α1 therapy on the function of CD4+CD25+CD127dim/- regulatory T (Treg) cells in chronic hepatitis B (CHB) patients. MethodsA total of 67 CHB patients who were admitted to Department of Infectious Diseases in Shaanxi Provincial People′s Hospital from December 2016 to July 2017 were enrolled, among whom 38 patients received entecavir antiviral therapy (control group) and 29 received entecavir combined with thymosin α1 for injection (treatment group). Peripheral blood mononucleated cells were isolated before and after treatment, and flow cytometry was used to measure the percentage of CD4+CD25+CD127dim/- Treg cells. CD4+CD25+CD127dim/- Treg cells were purified and co-cultured with autologous CD4+CD25- T cells. CCK-8 assay was used to measure cell proliferation, and ELISA was used to measure the levels of cytokines. The t-test was used for comparison of related indices between the two groups, the chi-square test was used for comparison of categorical data. ResultsIn the control group, the percentage of CD4+CD25+CD127dim/- Treg cells was significantly reduced from 12.32%±1.22% at baseline to 8.85%±2.18% after 12 weeks of treatment (t=4.579, P=0.0005), while in the treatment group, this value was significantly reduced from 13.71%±2.32% at baseline to 9.26%±2.30% after 12 weeks of treatment (t=4.803, P=00003). The measurement of cytokines was performed for 17 patients in the control group and 21 in the treatment group. After 12 weeks of treatment, the control group showed no significant changes in cell proliferation and levels of cytokines in the co-culture system of Treg and CD4+CD25- T cells; the treatment group had a significant increase in cell count in the co-culture system [(3.66±0.95)×106 vs (207±0.51)×106, t=5.709, P<0.0001], as well as significant reductions in the levels of inhibitory cytokines interleukin-10 (4140±11.89 pg/ml vs 56.53±27.85 pg/ml, t=2.639, P=0.019) and interleukin-35 (122.9±9.98 pg/ml vs 130.0±15.98 pg/ml, t=2.459, P=0.028) and significant increases in the levels of antiviral cytokines interferon-α (297.5±83.56 pg/ml vs 235.6±6772 pg/ml, t=2.603, P=0.017) and interferon-γ (5.83±0.85 pg/ml vs 4.39±0.95 pg/ml, t=4.659, P=0.0004). ConclusionThymosin α1 can inhibit the level and immunosuppressive function of CD4+CD25+CD127dim/- Treg cells in CHB patients and improve their immune function.
【关键字】:肝炎, 乙型, 慢性; T淋巴细胞, 调节性; 胸腺素
【Key words】:hepatitis B, chronic; T-lymphocytes, regulatory; thymosin
【引证本文】:LI Y, TIAN Y, YANG XM, et al. Effect of thymosin α1 on the function of CD4+CD25+CD127dim/- regulatory T cells in chronic hepatitis B patients[J]. J Clin Hepatol, 2018, 34(5): 1011-1014. (in Chinese) 李彧, 田颖, 杨晓梅, 等. 胸腺肽α1对慢性乙型肝炎CD4+CD25+CD127dim/-调节性T淋巴细胞功能的影响[J]. 临床肝胆病杂志, 2018, 34(5): 1011-1014.

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