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Immunity. 2018 Jan 16;48(1):161-173.e5. doi: 10.1016/j.immuni.2017.11.025. Epub 2018 Jan 2.

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

Author information

1
Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon 34141, Republic of Korea.
2
Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea.
3
Department of Internal Medicine, Chung-Ang University Hospital, Seoul 06973, Republic of Korea.
4
Department of Surgery, College of Medicine, The Catholic University of Korea, Daejeon St. Mary's Hospital, Daejeon 34943, Republic of Korea.
5
Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea.
6
Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
7
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
8
Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon 34141, Republic of Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea. Electronic address: park3@kaist.ac.kr.
9
Department of Internal Medicine, Chung-Ang University Hospital, Seoul 06973, Republic of Korea. Electronic address: mdjoon@cau.ac.kr.
10
Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon 34141, Republic of Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea. Electronic address: ecshin@kaist.ac.kr.

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.

KEYWORDS:

CD8(+) T cells; IL-15; NKG2D; bystander activation; host injury; immunopathogenesis; viral hepatitis; virus

PMID:
29305140
DOI:
10.1016/j.immuni.2017.11.025
[Indexed for MEDLINE]
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