You H, Liu Y, Cong M, Ping W, You C, Zhang D, Mehta J L, Hermonat P L
Liver Research Center, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing, China.
J Viral Hepat. 2006 Sep;13(9):605-12. doi: 10.1111/j.1365-2893.2006.00734.x.
Hepatitis B virus (HBV) has been an increasing problem throughout the world and remains difficult to treat. But immunotherapeutic approaches offer new, effective treatments. Three recombinant adeno-associated virus (AAV) type 2 vectors, carrying one of the HBV S, C or X gene, were used to load (transduce) professional antigen-presenting dendritic cells (DC) for the purpose of stimulating cytotoxic T lymphocytes (CTL) in vitro. It was found that all three recombinant AAV/HBV antigen virus loaded DC at approximately 90% transduction efficiency. Most importantly, all three AAV-loaded DC stimulated rapid, antigen-specific and major histocompatibility complex (MHC)-restricted CTL. In vitro, these CTL killed (30-50%) synthetic antigen-positive autologous targets as well as HepG2 liver cell targets. In comparing the three antigens, it was found that AAV/HBV-C-derived CTL consistently had the highest killing efficiency. CTL derived from AAV/HBV-C-loaded DC also showed significantly higher killing of targets than that from bacterially generated C-protein-loaded DC. Further studies showed that AAV/HBV-C-derived CTL had higher interferon (IFN)-gamma. These data suggest that AAV/HBV antigen gene-loading of DC may be useful for immunotherapeutic protocols against HBV infection and that the HBV C antigen may be the most useful for this purpose.
乙肝病毒（HBV）在全球范围内一直是一个日益严重的问题，且治疗起来仍然困难重重。但免疫治疗方法提供了新的有效治疗手段。三种携带乙肝病毒S、C或X基因之一的重组2型腺相关病毒（AAV）载体，被用于转导专业的抗原呈递树突状细胞（DC），目的是在体外刺激细胞毒性T淋巴细胞（CTL）。结果发现，所有三种重组AAV/乙肝病毒抗原病毒转导DC的效率约为90%。最重要的是，所有三种携带AAV的DC都能刺激快速、抗原特异性且受主要组织相容性复合体（MHC）限制的CTL。在体外，这些CTL杀死了（30 - 50%）合成抗原阳性的自体靶细胞以及HepG2肝细胞靶细胞。在比较这三种抗原时，发现源自AAV/乙肝病毒C的CTL始终具有最高的杀伤效率。源自携带AAV/乙肝病毒C的DC的CTL对靶细胞的杀伤作用也明显高于源自细菌产生的C蛋白负载的DC。进一步研究表明，源自AAV/乙肝病毒C的CTL具有更高的干扰素（IFN）-γ。这些数据表明，DC的AAV/乙肝病毒抗原基因负载可能对针对HBV感染的免疫治疗方案有用，并且乙肝病毒C抗原可能最适用于此目的。
