HBV特异性抗原对HBV携带者T淋巴细胞免疫功能的影响  

Study on HBV antigens and IL-12 affecting T cell-mediated immunity in HBsAg carriers

作　　者：林炳亮[1] 谢冬英[1] 谢俊强[1] 张晓红[1] 梅咏予[1] 高志良[1] 

机构地区：[1]中山大学附属第三医院感染科,广州510630

出　　处：《中华肝脏病杂志》2011年第3期186-190,共5页Chinese Journal of Hepatology

基　　金：艾滋病和病毒性肝炎等重大传染病防治科技重大专项（2008ZX1002-005,2008ZX1002-007）;广东省科技计划项目（2007B060401001,2006B36005004）

摘　　要：目的通过分析不同类型HBV携带者外周血单个核细胞（PBMCs）的细胞免疫功能，分析HBV抗原对其的影响，探索HBV慢性感染的机制并寻求可能的免疫治疗方法。方法用不同的抗原和（或）细胞因子刺激培养的无症状HBV携带者PBMCs，酶联免疫吸附法检测细胞培养上清液中不同细胞因子的水平；流式细胞术检测PBMCs的细胞表型。对数据进行t检验分析和相关性分析。结果HBsAg刺激无症状HBV携带者PBMCs后产生的干扰素（IFN）g为（48．3±19．8）pg／ml，较健康对照人群低[（196．2±104．3）pg／ml（t=3．023，P〈0．05）]。HBsAg和HBcAg刺激HBeAg阳性患者PBMCs分泌的IFN γ水平分别为（50．4±51．6）pg／ml和（63．2±36．9）pg／ml，明显低于HBeAg阴性组[（86．2±42．3）pg／ml和（101．4±32．5）pg／ml]，t值分别为2．468和3．184，P值均〈0．05；HBeAg阳性患者组分泌白细胞介素（IL）-12 P70明显低于HBeAg阴性组（P〈0．05）；补偿外源性IL-12可明显促进HBV携带者PBMCs分泌IFN-γ（P〈0．01），IL-12协同HBV抗原可激活CD8＋CD45RA＋CCR7＋及CD8＋CD45RA CD62L＋细胞。结论HBeAg阳性患者PBMCs分泌IL-12减少，这可能是HBV携带者持续感染的重要原因；外源性IL-12可促进HBV携带者PBMCs中的中枢记忆性T淋巴细胞的免疫功能。Objective To investigate the effect of HBV antigens and pathological mechanism of chronic HBV infection by analyzing the cellular immune function of peripheral blood mononuclear cells （PBMCs） from HBsAg carriers. Methods PBMCs were prepared from individuals with chronic asymptomatic HBV infection and cultured in the presence of different antigens and/or cytokines. The levels of cytokines in culture supernatants were detected by ELISA method. The phenotype of the cells was detected by FACS. Results The levels of IFN γ secreted by PBMCs from HBsAg carriers were （48.3 ± 19.8） pg/ml, significantly lower than that from healthy controls （t = 3.023, P 〈 0.05）; The IFN γ produced by PBMCs from HBeAg positive patients due to HBsAg and HBcAg stimulation were （50.4 ± 51.6） pg/ml and （63.2 ± 36.9） pg/ml, significantly lower than that of HBeAg negative patients （t = 2.468 and 3.184, P 〈 0,05, respectively）. The IL-12p70 secreted by PBMCs from HBeAg positive patients was also significantly lower than that of HBeAg negative patients （P 〈 0.05）; Exogenous IL-12 promoted significantly PBMCs to secrete IFN γ（P 〈 0.01） and IL-12 combined with HBV antigens activated CDS＋CD45RA＋CCR7＋ and CD8＋CD45RACD62L＋ cells. Conclusion IL-12 secreted by PBMCs decreased in HBeAg positive patients, which may be the crucial reason of viral persistence in chronic HBV carders. Exogenous IL-12 combined with specific HBV antigen could promote the central memory CD8＋ T cells to produce IFN γ.

关 键 词：肝炎病毒 乙型 免疫 细胞 细胞因子类 

分 类 号：R512.62[医药卫生—内科学]