Immunopathology and therapy of chronic active hepatitis type B

研究了纯化的重组乙肝表面抗原(RHBs Ag)和核心抗原(RHBcAg)在体外对淋巴因子激活的杀伤细胞(LAK)活性的抑制作用。外周血单个核细胞(PBMC)与白细胞介素2(IL-2)、rHBs Ag或rHBcAg共同孵育72小时后，LAK细胞对Daudi细胞的杀伤活性显著降低。相比之下，含有大肠杆菌提取物的IL-2和单独使用IL-2都没有显示出显著的结果。此外，rHBs Ag和rHBcAg对K562细胞的NK细胞杀伤活性也有一定的抑制作用。众所周知，NK细胞和LAK细胞在宿主免疫监视中起着重要作用。用乙肝病毒基因产物修饰免疫监控可能会导致慢性乙肝病毒感染和肝细胞癌。…患者外周血单核细胞对重组HBcAg反应的研究H-HBV型感染越多。急性乙型肝炎和HBeAg阳性慢性活动性肝炎患者PBMCs对rHBcAg均有明显的增殖反应。外周血单核细胞增殖反应与血清转氨酶水平之间存在统计学相关性。在增殖反应中，CD4^+细胞对rHBcAg的反应好于CD8^+细胞。CD4~+细胞对HBcAg的特异性识别可能在人体清除HBVc方面起重要作用。我们最近的研究发现，即使在慢性活动性肝炎患者的外周血中也存在由CD4^+细胞介导的HBcAg特异性增强和CD8^+细胞介导的HBcAg特异性抑制，而在HBs健康携带者中则不存在。在乙肝病毒感染的不同阶段，CD4和CD8之间的细胞相互作用可能与肝细胞损伤程度有关。慢性乙肝的治疗仍然令人费解。然而，最近两年来，IL-2联合干扰素α以及干扰素α和γ的联合治疗得到了应用。这些疗法的疗效仍在考虑中，因为这些疗法的持续时间和随访都不令人满意。进一步的研究是必要的，以了解增强对清除乙肝病毒感染的人类肝细胞的特异性免疫反应。较少

Hepatitis B virus (HBV) may modify some immunological functions in patients with hepatitis B. In the present study, we have investigated the inhibitory effects of purified recombinant HBV surface antigen (rHBsAg) and core antigen (rHBcAg) on lymphokine-activated killer cell (LAK) activity in vitro. Peripheral blood mononuclear cells (PBMCs), which were preincubated with interleukin-2 (IL-2) or rHBsAg or rHBcAg for 72 hours, showed a significant decreased activity of LAK cells on cytotoxicity against Daudi cells. In contrast, both IL-2 with E. coli extracts and IL-2 alone demonstrated non-significant results. In addition, rHBsAg and rHBcAg showed depressed NK cell cytotoxicity against K562 cells. It is well known that NK and LAK cells play an important role in host immunosurveillance. Modification of immunosurveillance by HBV gene products may result in chronic HBV infection as well as hepatocellular carcinoma. The proliferation of PBMCs in response to rHBcAg was studied in patients wit … More h HBV infection. Significant proliferations of PBMCs to rHBcAg were detected in patients with acute hepatitis B as well as HBeAg positive chronic active hepatitis. A statistical correlation was found between proliferative responses of PBMCs and and serum transaminase levels. In proliferative response, CD4^+ cells responded well to rHBcAg in comparison to CD8^+ cells. The specific recognition of HBcAg by CD4^+ cells may play an important role in the clearance of HBV in humans. Our recent studies have revealed that HBcAg-specific enhancement mediated by CD4^+ cells and HBcAg-specific suppression mediated by CD8^+ cells are present even in the peripheral blood compartments in patients with chronic active hepatitis B, but not in HBs healthy carriers. Cell interactions between CD4 and CD8 in various stages of HBV infection may be responsible for the degree of hepatocellular injury. Treatment of chronic hepatitis B is still puzzling. However, recently, IL-2 therapy combined with interferon (IFN) alpha and combination therapy of IFN alpha and gamma have been applied for the last two years. Efficacy of these therapies are still under consideration, since duration of these therapies as well as follow-up was not satisfactory. Further studies are necessary to understand the enhancement of specific immune response to HBV clearing HBV-infected hepatocytes in humans. Less