IMMUNOLOGIC STUDIES IN PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬化的免疫学研究

• 批准号: 3855405
• 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/3855405
• 关键词: B lymphocyte; CD4 molecule; T lymphocyte; autoimmune disorder; biopsy; cellular immunity; cellular pathology; cytokine; human subject; human tissue; humoral immunity; immunoglobulin M; immunohematology; immunoregulation; immunosuppression; leukocyte activation /transformation; lymphokines; 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 other 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+, Leu-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 diseases, mRNA for IL-1,2,4,5 and 6, IFN-gamma and TNF-alpha were not detected in liver biopsies from patients with PBC. While these findings do not exclude a role for cytokines in the mediation of the 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.

原发性胆汁性肝硬化（PBC）似乎是一种模型自身免疫性疾病。 异常免疫机制正在研究这种疾病，但到目前为止， 疾病特异性免疫缺陷尚未确定。 以确定是否先前描述的淋巴细胞异常 PBC中的免疫调节性T细胞功能可能是由于免疫调节性T细胞功能的改变 T细胞的亚群、表型和功能特征， 在其表面上具有可检测的CD 4抗原（通过单克隆抗体） 进行了检查。 PBC患者的外周血淋巴细胞数量正常， CD 4+、Leu-8+ T细胞，但与其他肝硬化患者相比， 疾病、免疫球蛋白合成抑制和促分裂原刺激 由该T细胞亚群介导的增殖是有缺陷的。 PBC患者外周血CD 4+、Leu-8+ T细胞功能缺陷 被佛波酯纠正，表明细胞功能异常 涉及蛋白激酶C的生化途径可能有助于 PBC患者表现出的免疫异常。 相比 对照组非PBC慢性炎症性肝病患者， 肝脏中未检测到IL-1、2、4、5和6、IFN-γ和TNF-α PBC患者的活检组织。 虽然这些发现并不排除 细胞因子在PBC胆管病变中的介导作用， 表明非细胞因子介导的免疫损伤起着 在PBC疾病进展中的重要作用。