摘要
目的探讨细胞因子诱导的杀伤细胞(CIKs)治疗对乙肝病毒(HBV)的抑制作用及其机制。方法选取2009年4月-2010年12月于解放军302医院住院,且未经抗病毒药物及其他免疫治疗的慢性乙肝患者16例,采集外周血单个核细胞(PBMC)经细胞因子鸡尾酒诱导培养成CIK细胞后,经静脉回输患者体内。观察CIK细胞治疗后24周内患者体内HBV DNA水平、CD3+CD56+细胞频率的变化,以及髓样树突状细胞(mDCs)和浆样树突状细胞(pDCs)频率的改变。结果自体CIK回输后,9例患者产生病毒学应答,其体内HBV DNA水平分别于第41、2及24周(分别为5.70、5.09和4.08log10拷贝/ml)出现明显降低(P<0.05或P<0.01);7例患者表现为病毒学无应答,其体内HBV DNA水平均与在基线时(6.39log10拷贝/ml)无明显差异(P>0.05)。经14d的诱导培养后,病毒学应答者CIK细胞的主要效应细胞CD3+CD56+细胞比例为17.21%,明显高于无应答者(8.97%,P<0.05)。经CIKs治疗后,病毒学应答者pDCs频率由治疗前的0.27%上升至治疗后4周的0.39%(P<0.05)和治疗后12周的0.34%(P<0.05),而病毒学无应答者无明显改变。CIK细胞回输后无明显不良反应。结论 CIK细胞治疗慢性乙肝安全性好,能抑制HBV复制,其机制部分是通过提高pDCs频率实现的。
Objective To investigate the effect of cytokine-induced killer cells（CIKs） treatment on the suppression of HBV replication and its mechanism.Methods Sixteen patients with chronic hepatitis B（CHB）,hospitalized from Apr.2009 to Dec.2010 in 302 Hospital,having not received antiviral drugs treatment or immunotherapy,were enrolled in present study.The peripheral blood mononuclear cells（PBMC） were collected and induced into CIKs by cytokine cocktail,and transfused back to patients via intravenous injection.The effects of CIK-cell transfusion on HBV DNA load,changes of the cell frequency of CD3＋CD56＋,myeloid dendritic cells（mDCs） and plasmacytoid dendritic cells（pDCs） were observed during a 24-week follow-up period.Results After autologous CIKs transfusion,the level of HBV DNA decreased in 9 sustained virological responders at 4th,12th and 24th week（5.70,5.09 and 4.08log10 copies/ml,respectively,P0.05 or P0.01）.The HBV DNA level showed no difference compared with the baseline（6.39log10 copies/ml） in other 7 non-virological responders.After 14d of inducible cultivation,the frequency of CIK-CD3＋CD56＋ cells,which were the main effectors,was significantly higher in virological responders（17.2%） than in non-virological responders（9.0%,P0.05）.After CIKs transfusion,the frequency of pDC in virological responders increased from 0.27% at the baseline to 0.39% at 4-week and 0.34% at 8-week（P0.05）,but no differences were found in non-virological responders during the follow up period.No serious clinical adverse effects were observed.Conclusions CIKs treatment can effectively inhibit the HBV replication,and it is safe for CHB patients.The mechanism of CIKs treatment on the suppression of HBV is partially attributable to the increased frequency of pDCs.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2011年第9期901-903,共3页
Medical Journal of Chinese People's Liberation Army
