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.

急性甲型肝炎（AHA）涉及严重的CD8 ⁺ T细胞介导的肝损伤。在这里，我们显示了在AHA期间，特定于无关病毒的CD8 ⁺ T细胞被激活了。甲型肝炎病毒（HAV）感染的细胞产生IL-15，该IL-15诱导记忆CD8 ⁺ T细胞的T细胞受体（TCR）独立激活。如NKG2D上调所表明的，在患者中检测到非HAV特异性CD8 ⁺ T细胞的TCR依赖性激活，IL-15是非TCR依赖性T细胞激活的标志。CD8 ⁺来自AHA患者的T细胞在没有TCR参与的情况下通过激活受体NKG2D和NKp30触发了先天性细胞毒性。我们证明了肝损伤的AHA患者的严重程度与病毒特异性HAV-无关CD8的激活相关⁺ T细胞和CD8的先天样细胞杀伤活性⁺ T细胞，但没有具体的HAV-T细胞的活化。因此，AHA中的宿主损伤与旁观者激活的CD8 ⁺ T细胞的先天性细胞毒性有关，这对急性病毒性疾病具有影响。