TLR3对乙型肝炎疫苗无弱应答婴儿脐血单个核细胞 Th1/Th2型细胞因子的影响  

The effects of TLR3 up-regulation on Th1/Th2 cytokines in CBMCs of infants with non/hypo response to hepatitis B vaccine

作　　者：张睿君 扆琳珠 武佳欣 赵甜静 李雁笛 王婷[1] 汪波[2] 丰淑英 冯永亮[1] 王素萍[1] ZHANG Rui-jun;YI Lin-zhu;WU Jia-xin;ZHAO Tian-jing;LI Yan-di;WANG Ting;WANG Bo;FENG Shu-ying;FENG Yong-liang;WANG Su-ping(Department of Epidemiology,Shanxi Medical University,Taiyuan 030001,China;Department of Obstetrics and Gynecology,the Third People s Hospital of Taiyuan,Taiyuan 030012,China)

机构地区：[1]山西医科大学流行病学教研室,太原030001 [2]太原市第三人民医院妇产科,太原030012

出　　处：《中华疾病控制杂志》2020年第6期711-715,722,共6页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(81573212;81872677);传染病预防控制国家重点实验室自主研究开放课题(2017SKLID306;2018SKLID310)。

摘　　要：目的探索能否通过上调乙型肝炎病毒表面抗原(hepatitis B surface antigen,HBsAg)阳性母亲脐血单个核细胞(cord blood mononuclear cells,CBMCs)TLR3改变其Th1/Th2型细胞因子表达水平及其程度。方法收集40例HBsAg阳性母亲脐血,分离CBMCs进行体外实验,分对照组、HBV(hepatitis B virus,HBV)刺激组和聚肌苷酸胞苷酸(polyinosinic-polycytidylic acid,Poly I∶C)+HBV刺激组。用流式细胞术和酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)分别检测TLR3蛋白和Th1/Th2型细胞因子水平,以化学发光免疫分析法测定婴儿12月龄外周血抗-HBs水平判定乙型肝炎疫苗(简称乙肝疫苗)应答情况。结果经TLR3激动剂协同HBV干预后,乙肝疫苗无/弱应答者CBMCs TLR3上升37.41%,高于强应答者(22.48%)(P=0.262),Th1/Th2型细胞因子表达水平均低于强应答者(均有P<0.001)。HBV刺激可下调Th1/Th2型细胞因子表达水平,Poly I∶C+HBV刺激可上调Th1/Th2型细胞因子表达水平(均有P<0.05);经Poly I∶C+HBV刺激后,无/弱应答者γ干扰素(interferon-γ,IFN-γ)、白细胞介素4(interleukin 4,IL-4)和白细胞介素10(interleukin 10,IL-10)表达水平接近强应答者HBV刺激后的表达水平(均有P>0.05)。结论 HBV感染对HBsAg阳性母亲婴儿的免疫损伤与乙肝疫苗无/弱应答可能有关,上调CBMCs TLR3蛋白表达水平可以提高无/弱应答者Th1/Th2型细胞因子表达水平。Objective To explore whether TLR3 up-regulation could change the Th1/Th2 cytokines expression in CBMCs of HBsAg-positive maternal infants with different hepatitis B vaccine immune status. Methods Umbilical cord blood of 40 HBsAg-positive mothers was collected. CBMCs were separated and divided into control group, HBV stimulation group and Poly I∶C+HBV stimulation group. The protein of TLR3 and Th1/Th2 cytokines were detected by flow cytometry and ELISA, respectively. The anti-HBs level of peripheral blood from infants at 12 months of age were detected by chemiluminescence immunoassay to determine the immune response of hepatitis B vaccine. Results Stimulated with TLR3 agonist and HBV, the increased rate of TLR3 in CBMCs of infants with non/hypo response to hepatitis B vaccine(37.41%) was higher than that of infants with high response(22.48%)(P=0.0262), the levels of Th1/Th2 cytokines were lower than those of infants with high response(all P<0.001). Th1/Th2 cytokines expression levels decreased after HBV stimulation, and increased after Poly I∶C+HBV stimulation(P<0.05). IFN-γ, IL-4 and IL-10 levels of non/hypo responders after Poly I∶C+HBV stimulation were close to those of high responders after HBV stimulation(all P>0.05). Conclusions HBV could damage the immune status of HBsAg-positive maternal infants and may be related to the non/hypo response to hepatitis B vaccine. The expression of Th1/Th2 cytokines in non/hypo-response infants may increase when the TLR3 protein in CBMCs is up-regulated.

关 键 词：TOLL样受体3 TH1/TH2型细胞因子 乙型肝炎疫苗 无/弱应答 

分 类 号：R749.4[医药卫生—神经病学与精神病学]