The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid: a mechanism for persistence.
The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid: a mechanism for persistence.
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DOI：
10.4049/jimmunol.160.4.2013
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发表时间：
1998-02
影响因子：
4.4
通讯作者：
D. Milich;Margaret K. Chen;J. Hughes;Joyce E. Jones
中科院分区：
文献类型：
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作者：
D. Milich;Margaret K. Chen;J. Hughes;Joyce E. Jones
B型肝炎前核心抗原（HBeAg）是B型肝炎核心抗原（HBcAg）的分泌型非颗粒形式，其功能尚不清楚。一定比例的HBeAg特异性Th细胞逃避HBeAg转基因（Tg）小鼠中的缺失/无反应性，并在体内用适当的Th细胞肽激活后介导抗HBe“自身抗体”（autoAb）的产生。该模型系统用于确定分泌型HBeAg如何影响外周Th细胞的缺失。为此，将HBeAg-Tg小鼠与Fas和Fas配体（FasL）缺陷型lpr/lpr和gld/gld突变小鼠繁殖。Fas-FasL相互作用介导外周活化诱导的细胞凋亡。在HBeAg-Tg/+小鼠中，产生了高滴度的抗HBe自身抗体，其仅由IgG 1同种型组成（即，Th 2-样轮廓）。相比之下，HBeAg-Tg/lpr和HBeAg-Tg/gld小鼠产生的抗-HBe autoAb显著较少，并且IgG同种型模式扩大到包括IgG 2a、IgG 2b和IgG 3以及IgG 1（即，混合的Th 1/Th 2样分布）。这些结果表明，HBeAg特异性Th 1细胞优先消耗Fas-FasL介导的相互作用。还通过将HBe/HBcAg特异性Th细胞转移到表达HBeAg和HBcAg的Tg受体小鼠中来检测循环HBeAg对HBcAg特异性Th 1细胞的影响。血清HBeAg的存在消除了预期的Th 1介导的抗HBc抗体应答，并使其向Th 2表型转变。这些结果表明，在B型肝炎病毒感染的背景下，循环HBeAg有可能优先消耗病毒清除所必需的炎性HBeAg和HBcAg特异性Th 1细胞，从而促进B型肝炎病毒的持续存在。
The hepatitis B precore Ag (HBeAg) is a secreted nonparticulate version of the viral nucleocapsid hepatitis B core Ag (HBcAg), and its function is unknown. A proportion of HBeAg-specific Th cells evade deletion/anergy in HBeAg-transgenic (Tg) mice and mediate anti-HBe "autoantibody" (autoAb) production after in vivo activation with the appropriate Th cell peptide. This model system was used to determine how secretory HBeAg may effect deletion of Th cells in the periphery. For this purpose, HBeAg-Tg mice were bred with Fas and Fas ligand (FasL)-defective lpr/lpr and gld/gld mutant mice. Fas-FasL interactions mediate activation-induced apoptosis in the periphery. In HBeAg-Tg/+ mice, high-titrated anti-HBe autoAb was produced that was exclusively composed of the IgG1 isotype (i.e., Th2-like profile). In contrast, HBeAg-Tg/lpr and HBeAg-Tg/gld mice produced significantly less anti-HBe autoAb, and the IgG isotype patterns were broadened to include IgG2a, IgG2b and IgG3 as well as IgG1 (i.e., mixed Th1/Th2-like profile). These results suggest that HBeAg-specific Th1 cells are preferentially depleted by Fas-FasL-mediated interactions. The effect of circulating HBeAg on HBcAg-specific Th1 cells was also examined by transferring HBe/HBcAg-specific Th cells into dual HBeAg- and HBcAg-expressing Tg recipient mice. The presence of serum HBeAg ablated the expected Th1-mediated anti-HBc Ab response and shifted it toward a Th2 phenotype. These results suggest that in the context of a hepatitis B viral infection, circulating HBeAg has the potential to preferentially deplete inflammatory HBeAg- and HBcAg-specific Th1 cells that are necessary for viral clearance, thereby promoting hepatitis B virus persistence.