趋化因子受体CXCR3及初始/记忆T淋巴细胞在原发性胆汁性肝硬化患者肝脏和外周血的变化

目的：通过研究PBC患者与NASH（非酒精性脂肪性肝炎）患者外周血和肝脏内淋巴细胞及其活化状态（分子标记：HLADR+CD3+），初始T细胞（CD45RA）、记忆T细胞（CD45RO）及趋化因子受体CXCR3，了解肝内淋巴细胞活化状态及其影响因素。方法：流式细胞法检测两种肝病患者外周血和肝内淋巴细胞分子标记CD3、CD4、CD8、HLADR+CD3+、CD45RA、CD45RO、CXCR3，统计分析。结果：PBC患者在外周血中以CD4＋T淋巴细胞为主，肝内浸润淋巴细胞CD8＋T和CD4＋T淋巴细胞无明显差异；肝内与外周血比较：CD4＋T淋巴细胞明显减少，CD4/CD8比例明显降低， HLADR+CD3+T淋巴细胞无显著性差异，CD45RA明显低于外周血，CD45RO则无显著性差异。CXCR3高于外周血中。与NASH比较：PBC患者肝内CD4＋T细胞增多；CD4/CD8上升，HLADR+CD3+增高，CD45RO、CD45RA减少，CXCR3增多；外周血T淋巴细胞及HLADR+CD3+两组间无显著差异。CD45RA减少，CXCR3两组间无显著性差异。结论：PBC患者外周血淋巴细胞及其活化状态与肝内免疫状况有关；肝内CD4+T淋巴细胞较NASH增多，提示CD4+T的活化和增殖是PBC发生和发展的关键环节；记忆性T淋巴细胞数量（CD45RO）控制在一定范围内可能是自身免疫反应得以不断进行的原因；CXCR3与T淋巴细胞向肝脏定向迁徙有关。

The variation of CXCR3 and CD45RA, CD45RO between liver infiltrating lymphocytes and peripheral blood mononuclear cells in primary biliary cirrhosis

Objective To explore the state of activation lymphocyte and influential factor of PBC patients. Methods CD3, CD4, CD8，CD4/CD8, HLADR+CD3+，CD45RA, CD45RO and CXCR3 of intrahepatic and PBL in PBC patients and NASH patients were detected with flow cytometric analysis. Results CD4+ T cells are the most abundant lymphocytes in the blood in PBC, while CD8+ and CD4+ T lymphocytes are the main subsets in the liver. Compared to the lymphocytes in the blood of PBC patients, the frequency of CD4+ T cells and CD45RA in the liver was lower; the ratio of CD4 and CD8 was decreased. No significant differences were found in the frequency of HLADR+CD3+ and CD45RO. Furthermore, CXCR3 were expressed at significantly higher frequencies in IHL than in PBL. Compared to the lymphocytes of NASH patients in the liver, the frequency of CD4+ T cells and HLADR+CD3+, the ratio of CD4 and CD8 was increased in PBC patients. The frequencies of CD45RA and CD45RO were decreased. CXCR3 were expressed at significantly higher frequencies in IHL in PBC patients. Compared to the lymphocytes of NASH patients in the blood, no significant differences were found in the frequency of HLADR+CD3+ in PBC patients. The frequency of CD45RA decreased. No significant differences were found of the expression of CXCR3. Conclusion We concluded that the state of activation lymphocyte in PBL relates to the immune state of liver. The activation and proliferation of CD4+ T cells in the liver may be the critical element of PBC. CXCR3 may play an important role in trafficking T lymphocyte to liver. The number of memory T lymphocyte which be controlled to some extend maybe one reason that autoimmune response could be continue.