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

Authors
 Jihye Kim  ;  Dong-Yeop Chang  ;  Hyun Woong Lee  ;  Hoyoung Lee  ;  Jong Hoon Kim  ;  Pil Soo Sung  ;  Kyung Hwan Kim  ;  Seon-Hui Hong  ;  Wonseok Kang  ;  Jino Lee  ;  So Youn Shin  ;  Hee Tae Yu  ;  Sooseong You  ;  Yoon Seok Choi  ;  Insoo Oh  ;  Dong Ho Lee  ;  Dong Hyeon Lee  ;  Min Kyung Jung  ;  Kyung-Suk Suh  ;  Shin Hwang  ;  Won Kim  ;  Su-Hyung Park  ;  Hyung Joon Kim  ;  Eui-Cheol Shin 
Citation
 Immunity, Vol.48(1) : 161-173.e5, 2018 
Journal Title
 Immunity 
ISSN
 1074-7613 
Issue Date
2018
Keywords
CD8(+) T cells ; IL-15 ; NKG2D ; bystander activation ; host injury ; immunopathogenesis ; viral hepatitis ; virus
Abstract
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S1074761317305265
DOI
10.1016/j.immuni.2017.11.025
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
김종훈(Kim, Jong Hoon) ORCID logo https://orcid.org/0000-0002-3385-8180
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162000
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