Discrepant Clinical Significance of CD28+CD8- and CD4+CD25high Regulatory T Cells During the Progression of Hepatitis B Virus Infection.
Discrepant Clinical Significance of CD28+CD8- and CD4+CD25high Regulatory T Cells During the Progression of Hepatitis B Virus Infection.
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DOI：
10.1089/vim.2018.0035
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发表时间：
2018-10
期刊：
影响因子：
2.2
通讯作者：
Xinghua Shen;Ping Xu;Xiang Yu;Hua-feng Song;Hui Chen;Xue-guang Zhang;Meiying Wu;Xue-Feng Wang
中科院分区：
文献类型：
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作者：
Xinghua Shen;Ping Xu;Xiang Yu;Hua-feng Song;Hui Chen;Xue-guang Zhang;Meiying Wu;Xue-Feng Wang
越来越多的证据表明，CD8+CD28-调节性T细胞在慢性病毒感染和肿瘤发生中增加。然而，目前尚不清楚它们在乙型肝炎病毒（HBV）感染中的特点。此外，尚不清楚这种调节性免疫亚群在对 HBV 感染进展的影响或关系方面是否与 CD4+CD25high 调节性 T 细胞不同。因此，我们研究了它们的动态，并比较了它们与 HBV 感染慢性和晚期阶段临床参数的相关性。数据显示，与健康对照相比，CD28+CD8-和CD4+CD25high T细胞的频率在慢性期和晚期均有所增加，而两个病例组之间没有显着差异。有趣的是，我们发现在慢性期，CD8+CD28-亚群的频率分别与丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）的水平呈负相关，并且与HBV DNA载量无关，而CD4+CD25high T细胞的频率分别与HBV DNA载量以及ALT和AST水平呈正相关。令人惊奇的是，在晚期阶段，CD4+CD25high T细胞的频率分别与HBV DNA载量和ALT水平呈负相关，而CD8+CD28-亚群的频率与这些临床参数之间没有显着相关性。因此，我们的研究结果表明，CD28+CD8-和CD4+CD25高调节性T细胞可能在HBV感染的不同阶段对调节抗病毒免疫反应和减轻免疫介导的肝损伤发挥独特的作用，这代表了基于进一步探索详细机制的HBV感染患者的潜在预后标志物和治疗靶点。
Accumulating evidence demonstrates that CD8+CD28- regulatory T cells increase in chronic viral infection as well as tumorigenesis. However, it is still not clear about their characteristics in hepatitis B virus (HBV) infection. In addition, it is not understood whether this regulatory immune subset is distinct from CD4+CD25high regulatory T cells in the aspect of impact on or relationship to the progression of HBV infection. Hence, we investigated their dynamics and compared their correlations with clinical parameters in the chronic and advanced phases of HBV infection. The data showed that compared with healthy controls, the frequencies of CD28+CD8- and CD4+CD25high T cells increased in both chronic and advanced phases, while there is no significant difference between the two case groups. Interestingly, we found that in chronic phase, the frequency of CD8+CD28- subset was negatively correlated with the levels of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST), respectively, and did not present association with HBV DNA load, whereas that of CD4+CD25high T cells was positively correlated with HBV DNA load and the levels of ALT and AST, respectively. Amazingly, in advanced phase, the frequency of CD4+CD25high T cells was negatively correlated with HBV DNA load and the levels of ALT, respectively, while there is no significant correlation between the frequency of CD8+CD28- subset and those clinical parameters. Thereby, our findings demonstrated that CD28+CD8- and CD4+CD25high regulatory T cells might exert distinct effect on modulating antiviral immune responses and mitigate immunomediated liver damage in different phases of HBV infection, which represent potential prognostic markers and therapeutic targets for HBV-infected patients based on further exploration of detailed mechanism.