Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A
Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A
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DOI：
10.1016/j.immuni.2017.11.025
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发表时间：
2018-01-16
期刊：
影响因子：
32.4
通讯作者：
Shin, Eui-Cheol
中科院分区：
文献类型：
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作者：
Kim, Jihye;Chang, Dong-Yeop;Shin, Eui-Cheol
急性甲型肝炎(AHA)涉及CD8(+)T细胞介导的严重肝损伤。我们在此展示了在AHA期间，针对无关病毒的CD8(+)T细胞被激活。甲型肝炎病毒(HAV)感染的细胞产生IL-15，诱导T细胞受体(TCR)非依赖的记忆性CD8(+)T细胞激活。在患者中检测到非甲型肝炎病毒特异性CD8(+)T细胞的TCR非依赖性激活，NKG2D上调，这是IL-15激活TCR非特异性T细胞的标志。AHA患者来源的CD8(+)T细胞通过激活受体NKG2D和NKp30而发挥天然的细胞毒作用，而不需要TCR的参与。我们证明AHA患者肝损伤的严重程度与甲型肝炎病毒无关的CD8(+)T细胞的激活和CD8(+)T细胞的天然类细胞杀伤活性有关，而与甲型肝炎病毒特异性T细胞的激活无关。因此，AHA的宿主损伤与旁观者激活的CD8(+)T细胞的先天类细胞毒性有关，这一结果与急性病毒性疾病有关。
Acute hepatitis A (AHA) involves severe CD8(+) T cell-mediated liver injury. Here we showed during AHA, CD8(+) T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8(+) T cells. TCR-independent activation of non-HAV-specific CD8(+) T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8(+) T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV-unrelated virus-specific CD8(+) T cells and the innate-like cytolytic activity of CD8(+) T cells, but not the activation of HAV-specific T cells. Thus, host injury in AHA is associated with innate-like cytotoxicity of bystander-activated CD8(+) T cells, a result with implications for acute viral diseases.