Milich D R
Scripps Research Institute, Department of Molecular Biology, La Jolla, CA 92037, USA.
J Viral Hepat. 1997;4 Suppl 2:48-59. doi: 10.1111/j.1365-2893.1997.tb00180.x.
Serological and biochemical studies indicate that acute HBV infection is resolved in the context of an efficient cell-mediated immune (CMI) response, whereas, chronic infection is characterized by weak to undetectable CMI responses and relatively efficient humoral immunity. Because humoral immunity and CMI are regulated by different TH subsets, factors which influence the induction of TH1 vs TH2 cells specific for the HBV nucleocapsid antigens (HBcAg, HBeAg) were examined in a murine model system. The factors which affected the HBc/HBeAg-specific TH1/TH2-cell balance included: (1) the structure of the antigen (i.e. HBcAg vs HBeAg); (2) the host MHC and T-cell site recognized; (3) crossregulation between TH1 and TH2 cells; (4) T-cell tolerance, which is more complete in TH1 than in TH2 cells; (5) secreted HBeAg, which preferentially depletes TH1 cells; (6) the HBV-specific subset response could be skewed towards either TH1 or TH2 predominance by cytokine treatment in vivo. The results suggest that the balance between TH1 and TH2 cells specific for the HBc/HBeAgs may be relevant in acute and chronic HBV infections. Importantly, HBeAg-specific TH2 cells preferentially evade tolerance induction as compared to their TH1-cell counterparts. Because HBeAg may act as a tolerogen during the vertical transmission of chronic HBV infection and preferentially depletes TH1 cells in the circulation, the predominance of HBeAg-specific TH2 cells may influence the initiation or maintenance of the chronic carrier state. In this case, cytokine therapy designed to shift a TH2-like response toward TH1 predominance (i.e. IL-12) may be beneficial in the treatment of chronic HBV infection.
血清学和生物化学研究表明，急性乙肝病毒感染在有效的细胞介导免疫（CMI）反应的背景下得以解决，而慢性感染的特征是CMI反应微弱甚至无法检测到，且体液免疫相对有效。由于体液免疫和CMI由不同的TH亚群调节，因此在小鼠模型系统中研究了影响针对乙肝病毒核衣壳抗原（HBcAg、HBeAg）的TH1与TH2细胞诱导的因素。影响HBc/HBeAg特异性TH1/TH2细胞平衡的因素包括：（1）抗原的结构（即HBcAg与HBeAg）；（2）宿主MHC和识别的T细胞位点；（3）TH1和TH2细胞之间的交叉调节；（4）T细胞耐受性（TH1细胞比TH2细胞更完全）；（5）分泌的HBeAg，其优先消耗TH1细胞；（6）体内细胞因子治疗可使乙肝病毒特异性亚群反应偏向TH1或TH2占优势。结果表明，针对HBc/HBeAgs的TH1和TH2细胞之间的平衡可能与急性和慢性乙肝病毒感染有关。重要的是，与TH1细胞对应物相比，HBeAg特异性TH2细胞优先逃避耐受性诱导。由于HBeAg在慢性乙肝病毒感染的垂直传播过程中可能作为一种耐受原，并优先消耗循环中的TH1细胞，HBeAg特异性TH2细胞的优势可能影响慢性携带者状态的起始或维持。在这种情况下，旨在将类似TH2的反应转变为TH1占优势（即IL-12）的细胞因子治疗可能对慢性乙肝病毒感染的治疗有益。
