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目的分析慢性乙型肝炎(CHB)患者外周血中CD8+T细胞及其亚群表面程序性死亡受体-1(PD-1)表达的变化特征及其临床关联性。方法用流式细胞术检测14例CHB患者和15例健康对照者外周血中CD8+T细胞及其亚群初始T细胞(TN)、中央记忆T细胞(TCM)、效应记忆T细胞(TEM)、终末效应记忆T细胞(TEMRA)的频数及细胞表面PD-1的表达水平,同时收集患者一般资料、生化指标和乙型肝炎病毒(HBV)病毒学指标等临床资料。使用SAS 9.1统计软件分析数据,应用Mann-Whitney U test分析组间差异,应用Spearman秩相关进行相关性分析,P<0.05为差异有统计学意义。结果与健康对照组相比,CHB患者的TEMRA亚群在CD8+T细胞中的频数显著降低(P=0.012),总CD8+T细胞(P=0.018)及其TEM亚群(P=0.004)表面PD-1的表达水平显著上升。相关性研究显示,CD8+TEM细胞表面PD-1的表达水平与HBV DNA载量呈显著正相关(r=0.554,P=0.040)。结论 CHB患者外周血中PD-1阳性的CD8+TEM频数升高,且与外周血中HBV DNA载量呈正相关,提示慢性乙型肝炎患者机体内HBV复制的活跃性可能与外周血中CD8+T细胞的活化状态,特别是其TEM亚群上PD-1的高表达关联。
Objective To analyze the changes of CD8 + T cells and PD-1 expression on peripheral blood of patients with chronic hepatitis B (CHB) and their clinical relevance. Methods Flow cytometry was used to detect CD8 + T cells and their subsets of initial T cells (TN), central memory T cells (TCM), effector memory T cells (TEMs) in 14 CHB patients and 15 healthy controls. , Frequency of terminal effector memory T cells (TEMRA) and cell surface expression of PD-1. Meanwhile, clinical data such as general data, biochemical indexes and HBV virological indexes were collected. SAS 9.1 statistical software was used to analyze the data. Mann-Whitney U test was used to analyze the differences between groups. Spearman rank correlation was used to analyze the correlation. P <0.05 was considered statistically significant. Results The frequency of TEMRA subpopulation in CHB patients was significantly lower in CD8 + T cells than in healthy controls (P = 0.012), total CD8 + T cells (P = 0.018), and TEM subpopulation (P = 0.004) Surface PD-1 expression levels increased significantly. Correlation studies showed that PD-1 expression on CD8 + TEM cells was positively correlated with HBV DNA load (r = 0.554, P = 0.040). Conclusions The frequency of PD-1 positive CD8 + TEM in peripheral blood of patients with CHB is elevated and positively correlated with the level of HBV DNA in peripheral blood, which indicates that the activity of HBV replication in patients with chronic hepatitis B may be related to the level of CD8 + T cells, especially their high expression of PD-1 on the TEM subpopulation.