Identification of the association of CD28+CD244+Tc17/IFN-γ cells with chronic hepatitis C virus infection
Identification of the association of CD28+CD244+Tc17/IFN-γ cells with chronic hepatitis C virus infection
复制标题
CD28( ) CD244( ) Tc17/IFN-γ细胞与慢性丙型肝炎病毒感染关系的鉴定
DOI：
10.1002/jmv.26205
复制
发表时间：
2020-07-06
影响因子：
12.7
通讯作者：
Shao，Shengwen
中科院分区：
文献类型：
--
作者：
Han，Wenzheng;Li，Jiajia;Shao，Shengwen
CD 8 +T细胞在丙型肝炎病毒（HCV）感染患者中发挥多种复杂的免疫作用，包括抗病毒、调节和耗竭作用。一些CD 8 +T细胞亚群被证实与HCV感染密切相关，如TCM，TEM，TEMRA，Tc 17和CD 8 +Treg。在此，我们报告了一种新的产生白细胞介素（IL）-17/干扰素（IFN）-γ的CD 8 +T（Tc 17/IFN-γ）细胞亚群，其与HCV患者中的CD 28 + CD 244+细胞、IL-17水平和HCV RNA显著相关。在用PEG-IFN-α 2a加利巴韦林的早期治疗期间，这些Tc 17/IFN-γ细胞的不平衡可以部分恢复，血清丙氨酸转氨酶正常化，但天冬氨酸转氨酶不能。此外，我们还分析了不同结局患者在接受peg-IFN-α 2a+利巴韦林治疗4周后该T细胞亚群百分比的动态变化，发现恢复患者的CD 8 + CD 28 + CD 244 +T细胞百分比显著降低，而未恢复患者则无此变化。在体外，CD 28 + CD 244 +T细胞是在该轴中分泌IL-17和IFN-γ的唯一CD 8 +T细胞组，并且用抗CD 244抗体阻断显著降低细胞因子产生。综上所述，本研究表明，CD 28 + CD 244 + Tc 17/IFN-γ细胞的频率和调节功能可能在持续性HCV感染中发挥重要作用。
CD8+T cells play multiple and complex immunological roles including antiviral, regulatory, and exhaustive effects in hepatitis C virus (HCV) infected patients. Some CD8+T‐cell subsets were confirmed to be closely related to HCV infection such as TCM, TEM, TEMRA, Tc17, and CD8+Treg. Herein, we report a new subset of interleukin (IL)‐17/interferon (IFN)‐γ producing CD8+T (Tc17/IFN‐γ) cells that markedly correlate with CD28+CD244+cells, IL‐17 levels, and HCV RNA in HCV patients. During early treatment with peg‐IFN‐a2a plus ribavirin, the imbalance of these Tc17/IFN‐γ cells could be partially restored, together with normalized serum alanine aminotransferase but not aspartate transaminase. Also, we analyzed the dynamic change of the percentage of this T cells subset in patients with different outcome after 4‐week course of treatment with peg‐IFN‐a2a plus ribavirin and found that the percentage of CD8+CD28+CD244+T cells significantly decreased in recovered patients but not in nonrecovered patients. In vitro, CD28+CD244+T cells were the only CD8+T‐cell group that secreted both IL‐17 and IFN‐γ in this axis and blockade with anti‐CD244 antibodies significantly reduced cytokine production. Taken together, this study demonstrates that the frequency and regulatory functions of CD28+CD244+Tc17/IFN‐γ cells may play an important role in persistent HCV infection.