慢性乙型肝炎患者CD8^+记忆T细胞的检测分析

Reciprocal changes of naive and effector/memory CD8^+ T lymphocytes in chronic hepatitis B virus infection

目的探讨慢性乙型肝炎患者和急性乙型肝炎恢复期患者CD8+记忆T细胞的产生及分布特性,分析其临床意义。方法流式细胞术检测16例急性乙型肝炎恢复期患者、26例慢性乙型肝炎患者和18名健康人的外周血CD8+记忆T细胞亚群,以初始T细胞、中心记忆T细胞(TCM)、效应记忆T细胞(TEM)、终末分化效应细胞(TTEM)占总计数CD8+细胞数的百分比表示。结果与健康组、急性乙型肝炎恢复期组相比,慢性乙型肝炎组患者CD8+初始T细胞明显增加(P<0.001);TCM、TEM细胞亚群分布频率显著降低(P<0.001)。急性乙型肝炎恢复期组与健康组相比,TCM升高(t=2.34,P=0.03)。高病毒载量组慢性乙型肝炎TTEM百分比比中低病毒载量高(t=2.43,P=0.02)。无论肝炎活动期还是静止期,初始T细胞、TCM、TEM、TTEM百分比差异均无统计学意义。结论慢性乙型肝炎患者和急性乙型肝炎恢复期患者CD8+记忆T淋巴细胞亚群的比例存在明显差异,可能与体内抗原长期存在以及刺激的程度相关。从而导致清除病毒的能力下降,慢性化的形成。

ObjectiveTo determine the production and frequencies of CD8＋ memory T cells from patients with chronic infection of hepatitis B virus （HBV） and subjects recovering from acute hepatitis B.MethodsA total of 26 patients with chronic hepatitis B who were hospitalized in the second Hospital of Nanjing from November 2011 to April 2014 and 16 subjects recovering from acute hepatitis B during same time period were recruited in the study. The CD8＋ memory T cell subsets were analyzed by CD8, CD27, CCR7 and CD45RA staining and flow cytometry.Results In comparison to healthy subjects and patients recovering from acute hepatitis B, chronic hepatitis B patients showed higher percentages of naive CD8＋T lymphocytes, and lower percentages of Central memory T cell（TCM）, effector memory T cell（TEM）. The frequencies of CD8＋ Central memory T cell （TCM） subset were increased in patients recovering from acute hepatitis B, compared with healthy subjects. The frequencies of terminal effector memory was found to be significantly higher in patients with viral load （VL） greater than 107IU/ml than in those VL〈107 IU/ml. The ability of CD8＋T cell differentiation showed a negative correlation with disease activity as measured by serum alanine aminotransferase（ALT）.Conclusion There are significant difference in frequencies of antigen-specific CD8＋ TCM and TEM among people with chronic hepatitis B and recovering from acute hepatitis B, which may be correlated with antigen load in vivo and antigen specific cellular immune responses. This may result in impairment of the generation of functionally competent memory cells, and an inability to achieve control of HBV replication.