Boisvert Judie, Kunkel Eric J, Campbell James J, Keeffe Emmet B, Butcher Eugene C, Greenberg Harry B
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Hepatol. 2003 Jan;38(1):67-75. doi: 10.1016/s0168-8278(02)00328-8.
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, yet little is known about the intrahepatic immune response in end-stage patients. Chemokines and their receptors are important regulators of immunity, particularly in the migration and localization of circulating leukocytes within peripheral tissues.
This report provides a comprehensive comparison of the chemokine receptor and activation phenotype of the major leukocyte subsets present in end-stage HCV-infected and non-HCV infected livers.
Lymphocytes were purified from homogenized explant liver tissue and analyzed by flow cytometry.
NK cells are the predominant cell type, followed by T cells, B cells and NK-T cells, independent of HCV status. T cells displayed a memory phenotype and low levels of activation markers. CCR5, CXCR3 and CXCR6 were expressed on a large fraction of activated cells, while moderate to low expression of CCR2, CCR6 and CX(3)CR1 was observed. Several other tissue-specific and inflammatory chemokine receptors were absent from infiltrating lymphocytes.
These results identify the chemokine receptors present on infiltrating lymphocytes during end-stage liver disease and suggest that such infiltration is predominantly controlled by non-tissue-specific inflammatory chemokines, a situation that may be distinct from liver homing pathways under normal conditions.
丙型肝炎病毒（HCV）是慢性肝病的主要病因，但对于终末期患者肝内免疫反应的了解甚少。趋化因子及其受体是免疫的重要调节因子，特别是在循环白细胞在外周组织内的迁移和定位方面。
本报告全面比较了终末期HCV感染和未感染HCV的肝脏中主要白细胞亚群的趋化因子受体及激活表型。
从匀浆的肝外植体组织中纯化淋巴细胞，并通过流式细胞术进行分析。
无论HCV感染状态如何，自然杀伤细胞（NK细胞）都是主要的细胞类型，其次是T细胞、B细胞和自然杀伤T细胞（NK-T细胞）。T细胞表现出记忆表型和低水平的激活标志物。CCR5、CXCR3和CXCR6在大部分激活细胞上表达，而CCR2、CCR6和CX(3)CR1的表达水平为中度至低度。浸润淋巴细胞中未检测到其他几种组织特异性和炎性趋化因子受体。
这些结果确定了终末期肝病时浸润淋巴细胞上存在的趋化因子受体，并表明这种浸润主要由非组织特异性炎性趋化因子控制，这种情况可能与正常条件下的肝归巢途径不同。
