IMMUNOLOGIC STUDIES IN PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬变是一种典型的自身免疫性疾病。 目前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确定的定义。 以确定先前描述的淋巴细胞异常是否 PBC的功能可能是由于免疫调节T细胞功能改变所致 T细胞亚群、表型和功能特征 使它们的表面可以(通过单抗)检测到CD4抗原 都进行了检查。PBC患者被发现有正常数量的 CD4+、Leu-8+T细胞，但与其他肝病患者相比 疾病、免疫球蛋白合成抑制和丝裂原刺激 该T细胞亚群介导的增殖反应是有缺陷的。 PBC患者外周血中CD4+、Leu-8+T细胞功能缺陷 被佛波酯纠正，这表明细胞的异常功能 涉及蛋白激酶C的生化途径可能有助于 PBC患者的免疫异常。与之形成鲜明对比的是 对照组非PBC慢性炎症性肝病患者 在肝脏中未检测到IL-1、2、4、5和6、干扰素-γ和肿瘤坏死因子-α PBC患者的活组织检查。虽然这些发现并不排除 细胞因子在PBC胆管病变中的调节作用 提示非细胞因子介导的免疫损伤在 在PBC的疾病进展中起主要作用。

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.