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树突状细胞可有效地被 HBVsvp 冲击,并在小鼠中诱导特异性免疫反应。

Dendritic cells can effectively be pulsed by HBVsvp and induce specific immune reactions in mice.

机构信息

Medizin IV, Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

出版信息

Vaccine. 2010 Dec 16;29(2):200-6. doi: 10.1016/j.vaccine.2010.10.056. Epub 2010 Nov 2.

Abstract

Eradication of chronic Hepatitis B virus (HBV) infection, marked by HBs seroconversion, is very rarely achieved by treatment with nucleoside and nucleotide analogs. Therapeutic cell based approaches, like interferon therapy, have a higher chance of seroconversion. Dendritic cells (DC) are key players in the cellular immune response and have been shown to play an important role in controlling HBV infection. In this study, the potential of ex vivo activated DC to induce specific immune responses against HBV was examined. DC derived from bone-marrow of BALB/c or C56BL/6 mice were pulsed with HBV subviral particles (HBVsvp), derived from the HepG2.2.15 cell line. HepG2.2.15 produces subviral particles consisting of the HBc and HBs proteins. Thus, the entire "viral surface" is presented to DC to induce an immune reaction. In vitro pulsation with HBVsvp successfully activated bone-marrow derived DC, demonstrated by FACS analysis showing increased MHCII, CD 86 and CCR-7. Immunization of mice, via subcutaneous injection of the activated DC, induced HBV specific immune reactions which were measured by ELISA, ELISPOT and T-cell proliferation analysis. Vaccination with ex vivo activated DC may be a promising tool for therapeutic or prophylactic approaches against the Hepatitis B virus.

摘要

慢性乙型肝炎病毒 (HBV) 感染的消除,以 HBs 血清转换为标志,通过核苷(酸)类似物治疗很少能实现。基于细胞的治疗方法,如干扰素治疗,具有更高的血清转换机会。树突状细胞 (DC) 是细胞免疫反应的关键参与者,已被证明在控制 HBV 感染方面发挥重要作用。在这项研究中,研究了体外激活的 DC 诱导针对 HBV 的特异性免疫反应的潜力。从 BALB/c 或 C56BL/6 小鼠的骨髓中提取 DC,并使用来自 HepG2.2.15 细胞系的 HBV 亚病毒颗粒 (HBVsvp) 进行脉冲处理。HepG2.2.15 产生由 HBc 和 HBs 蛋白组成的亚病毒颗粒。因此,将整个“病毒表面”呈现给 DC 以诱导免疫反应。通过 FACS 分析显示 MHCII、CD86 和 CCR-7 增加,证明体外用 HBVsvp 脉冲处理成功激活了骨髓来源的 DC。通过 ELISA、ELISPOT 和 T 细胞增殖分析测量了小鼠的免疫接种,通过皮下注射激活的 DC 进行免疫接种,诱导了 HBV 特异性免疫反应。体外激活的 DC 疫苗接种可能是针对乙型肝炎病毒的治疗或预防性方法的有前途的工具。

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