Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Contributes to Host Injury during Viral Infection
During hepatitis A virus (HAV) infection, HAV-infected cells produce IL-15 that induces T cell receptor (TCR)-independent bystander activation of non-HAV-specific memory CD8+ T cells. These cells exert innate-like cytotoxicity triggered by NK-activating receptors without TCR engagement. Importantly, IL-15-induced bystander-activated CD8+ T cells contribute to host injury during acute viral infection through this cytotoxicity.
In the present study, we investigated the activation status and function of CD8+ T cells and the mechanisms by which CD8+ T cells mediate host injury in acute hepatitis A (AHA), which is caused by hepatitis A virus (HAV) infection and manifests as severe liver injury in adults. Though HAV-specific CD8+ T cells are thought to be responsible for liver injury in AHA, a recent study showed that HAV-specific CD8+ T cells do not exhibit effector function in HAV-infected chimpanzees. In this context, we examined HAV-specific and non-HAV-specific CD8+ T cells in AHA patients and studied a mechanism of immune-mediated liver injury in AHA.
In this study, researchers at KAIST demonstrate that CD8+ T cells specific to HAV-unrelated viruses are activated and proliferate during AHA. HAV-infected cells produced IL-15, which induced T cell receptor (TCR)-independent activation of CD8+ T cells. CD8+ T cells isolated from AHA patients exerted innate-like cytolytic activity, which was triggered by ligation of NKG2D and NKp30 without TCR engagement. We also showed that hepatocytes from HAV-infected liver overexpressed NKG2D ligands, making them potential cytolytic targets of bystander-activated HAV-unrelated virus-specific CD8+ T cells. Finally, we observed that liver injury during AHA is associated with innate-like cytotoxic function of bystander-activated CD8+ T cells.
Taken together, our results show a human viral disease in which host injury is associated with innate-like cytolytic activity of bystander-activated CD8+ T cells.
* lab webpage : http://www.cell.com/immunity/fulltext/S1074-7613(17)30526-5