PD-1受体在HBV—ACLF患者外周血CD8^＋T细胞上的表达研究

目的探讨乙型肝炎病毒所致慢加急性肝衰竭（HBV—ACLF）患者外周血中CD8^＋T细胞上PD-1（Programmed death-1）的表达以及对CD8^＋T细胞的影响。方法收集60例HBV—ACLF患者外周血；应用流式细胞仪检测外周血中CD8^＋淋巴细胞上的PD-1、CD95、穿孔素、颗粒酶A、颗粒酶B、CD107a的表达以及CD14细胞上PD—L1的表达；根据不同病情分期和不同预后比较各分子的表达差异；设15名肝硬化患者及15名健康人为对照组。结果（1）HBV-ACLF患者CD8^＋T细胞上PD-1较肝硬化组和健康组表达上调（P〈0．05）；好转组PD-1表达率低于无效组（P〈0．05）；早、中、晚三期PD-1表达率呈上升趋势（P〈0．05）；（2）PD—L1在好转组及病情早期表达相对最低；（3）PD-1与CD95在死亡组表达明显升高；穿孔素、颗粒酶及CD107a在死亡组表达升高，但PD-1在这三类细胞上表达率非常低。结论PD-1在HBV．ACLF患者外周血CD8^＋T细胞上表达上调，且与病情严重程度呈正比。其上调表达可能促进总CD8^＋T细胞的凋亡，但对于具有杀伤活性的CD8^＋T细胞抑制作用相对较弱。

Research of PD-1 expression in CD8~+ T cell of Peripheral blood with HBV-associated acute-onchronic liver failure

Objective To analyze PD-1 expression in CD8~+T cell of Peripheral blood with HBV-associated acute-on-chronic liver failure and effect on CD8~+T cell.Methods We selected 60 patients with HBV-ACLF and collected their peripheral blood.We analyzed the expressions of PD-1,CD95,perforin,granzyme A,granzyme B,CD107a on CD8~+T lymphocytes and the expression of PD-L1 on monocytes in peripheral blood by using flow cytometry.15 liver cirrhosis patients(LC) and 15 healthy individuals(HC) are control groups.Result PD-1 expression was (1)The PD-1 expression in HBV-ACLF patients was significantly elevated compared with those in HC and lower in improved group than that in invalid group and death group (P＜0.05) and increased from prophase,metaphase to advanced stage (P＜0.05).Moreover.(2)PD-L1 expression on monocytes was positively correlated with disease progression.(P＜0.05).(3)Both PD-1 and CD95 expressions were higher in dead group than those in improved and non-improved groups.Perforin,granzymes and CD107a expressions on CD8~+ T cells significantly increased in dead group compared with those in improved and non-improved groups (P＜0.05).However,PD-1 expressions on these cells were lower,compared with normal persons.Conclusions The expression of PD-1 and PD-L1 in HBV-ACLF patients was positively correlated with disease progression.The elevated PD-1 expression promoted apoptosis of CD8~+T ceils.For HBV-ACLF patients,the PD-1 expression on effector CD8~+T cells was lower than those in other CD8~+T cells,which maybe accounted for the failure to controlling immune injury in liver.