Innate-like Cytotoxic Function of Bystander-Activated CD8(+) T Cells Is Associated with Liver Injury in Acute Hepatitis A

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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.
Publisher
CELL PRESS
Issue Date
2018-01
Language
English
Article Type
Article
Citation

IMMUNITY, v.48, no.1, pp.161 - +

ISSN
1074-7613
DOI
10.1016/j.immuni.2017.11.025
URI
http://hdl.handle.net/10203/240096
Appears in Collection
MSE-Journal Papers(저널논문)
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