PD-1受体在HBV—ACLF患者外周血CD8^＋T细胞上的表达研究

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

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。

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 HBV-ACLF patients was positively correlated with Conclusions The expression of PD-1 and PD-L1 in disease progression. The elevated PD-1 expression promoted apoptosis of CD8 ^＋ T cells. For HBV-ACLF patients, the PD-1 expression on effector CD8 ^＋ T cells was lower than those in other CD8 ^＋ T ceils, which maybe accounted for the failure to controlling immune injury in liver.