Immunopathology and therapy of chronic active hepatitis type B

慢性活动性乙型肝炎的免疫病理学和治疗

基本信息

批准号：
01570402
负责人：
NISHIOKA Mikio
金额：
$ 1.34万
依托单位：
Kagawa Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570402/
关键词：
Hepatitis B virus HB core antigen Chronic active hepatitis Natural killer cells Lymphokine-activated killer cells Anti-viral therapy Interferon Interleukin-2 B型肝炎インタ-ロイキンz HBC抗原 Pre Sz抗原リンパ球 T細胞

项目摘要

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

乙型肝炎病毒（HBV）可能会改变乙型肝炎患者的一些免疫功能。在本研究中，我们研究了纯化的重组HBV表面抗原（rHBsAg）和核心抗原（rHBcAg）对淋巴因子激活的杀伤细胞的抑制作用与白细胞介素 2 (IL-2) 或 rHBsAg 预孵育的外周血单核细胞 (PBMC) 的体外活性。或rHBcAg 72小时，显示LAK细胞对Daudi细胞的细胞毒性活性显着降低，相反，IL-2与大肠杆菌提取物和单独的IL-2均表现出不显着的结果。降低 NK 细胞对 K562 细胞的细胞毒性众所周知，NK 和 LAK 细胞在 HBV 免疫监视的调节中发挥着重要作用。基因产物可能导致慢性 HBV 感染以及肝细胞癌。在 HBV 感染患者中研究了 PBMC 响应 rHBcAg 的增殖。在急性乙型肝炎和肝细胞癌患者中检测到 PBMC 显着增殖。 HBeAg 阳性慢性活动性肝炎在 PBMC 的增殖反应和血清转氨酶水平之间发现了统计相关性。与 CD8^+ 细胞相比，CD4^+ 细胞对 rHBcAg 反应良好 CD4^+ 细胞对 HBcAg 的特异性识别可能在人类 HBV 清除中发挥重要作用。由 CD4^+ 细胞介导的 HBcAg 特异性抑制甚至在慢性活动性乙型肝炎患者的外周血区室中也存在，但在健康的 HBs 中则不存在HBV感染各个阶段CD4和CD8之间的细胞相互作用可能是导致慢性乙型肝炎的治疗方法仍然令人费解，然而，最近，IL-2联合干扰素(IFN)和联合治疗。过去两年一直在应用干扰素α和γ疗法，因为这些疗法的持续时间和随访情况并不令人满意，需要进一步研究来了解特异性免疫的增强情况。人类对 HBV 清除 HBV 感染的肝细胞的反应较少。