IMMUNOLOGIC STUDIES IN PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬化的免疫学研究

• 批准号: 3840477
• 负责人: E ANTHONY JONES
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3840477
• 关键词: B lymphocyte; CD4 molecule; T lymphocyte; antibody formation; autoimmune disorder; biliary tract disorder; biopsy; cell population study; cellular immunity; cellular pathology; cytokine; helper T lymphocyte; human subject; human tissue; humoral immunity; immunochemistry; immunoglobulin M; immunohematology; immunoregulation; immunosuppression; laboratory mouse; leukocyte activation /transformation; liver cirrhosis; lymphocyte proliferation; mixed lymphocyte reaction test; monoclonal antibody; orphan disease /drug; phorbols; primary biliary cirrhosis; protein kinase C; suppressor T lymphocyte; tissue /cell culture

Primary biliary cirrhosis (PBC) appears to be a model autoimmune disease. Abnormal immune mechanisms are being studied in this disease, but so far a disease-specific immunologic deficit has not been defined with certainty. To determine whether previously described abnormalities of lymphocyte function in PBC might be due to altered function of immunoregulatory T cell subpopulations, phenotypic and functional characteristics of T cells that have the CD4 antigen detectable (by monoclonal antibody) on their surface were examined. Patients with PBC were found to have normal numbers of CD4+, Leu-8+ T cells, but, in contrast to patients with liver diseases, suppression of immunoglobulin synthesis and mitogen-stimulated proliferation mediated by this subpopulation of T cells were defective. These defects in the function of CD4+, Lei-8+ T cells in patients with PBC were corrected by phorbol ester suggesting that abnormal function of the biochemical pathway involving protein kinase C may contribute to the immunological abnormalities exhibited by patients with PBC. In contrast to control patients with non-PBC chronic inflammatory liver disease, mRNA for IL- 1,2,4,5 and 6, and TNF-alpha were not detected in liver biopsies from patients with PBC. mRNA for INF-gamma was detected in 11 of 18 PBC liver biopsies. While these findings do not exclude a role for cytokines in the mediation of bile duct lesions in PBC, they suggest that immunologic injury that is not mediated by cytokines plays a major role in disease progression in PBC.

原发性胆汁性肝硬变(PBC)似乎是一种自身免疫模型 疾病。人们正在研究这种疾病的异常免疫机制， 但到目前为止，疾病特异性免疫缺陷还没有被定义。 肯定会的。以确定之前描述的异常是否 PBC中淋巴细胞功能的改变可能是由于PBC的功能改变 免疫调节性T细胞亚群，表型和功能 具有可检测到的CD4抗原的T细胞的特征(通过 检测其表面的单抗)。PBC患者 发现有正常数量的CD4+，Leu-8+T细胞，但在 与肝病患者相比，免疫球蛋白抑制 合成及其介导的丝裂原刺激的增殖 T细胞亚群存在缺陷。这些功能上的缺陷 佛波醇对PBC患者外周血中CD4+、Lei-8+T细胞的影响 Ester提示生化途径的异常功能 蛋白激酶C的参与可能有助于免疫学 PBC患者表现出的异常。与对照形成对比 非PBC慢性炎症性肝病患者IL-1mRNA的检测 肝活检组织中未检测到1、2、4、5、6和肿瘤坏死因子-α。 PBC患者。18例PBC肝组织中有11例检测到干扰素-γ的mRNA 活组织检查。虽然这些发现并不排除细胞因子在 胆管病变在PBC中的中介作用，提示免疫学 非细胞因子介导的损伤在疾病中起主要作用 PBC的进展。