장동엽 (KAIST)

한빛사논문

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KAIST

Immunity, Published: January 2, 2018, DOI: http://dx.doi.org/10.1016/j.immuni.2017.11.025 Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A

Jihye Kim,^1,8 Dong-Yeop Chang,^2,8 Hyun Woong Lee,^3,8 Hoyoung Lee,^1,8 Jong Hoon Kim,² Pil Soo Sung,² Kyung Hwan Kim,² Seon-Hui Hong,¹ Wonseok Kang,² Jino Lee,² So Youn Shin,² Hee Tae Yu,² Sooseong You,² Yoon Seok Choi,² Insoo Oh,² Dong Ho Lee,⁴ Dong Hyeon Lee,⁵ Min Kyung Jung,² Kyung-Suk Suh,⁶ Shin Hwang,⁷ Won Kim,⁵ Su-Hyung Park,^1,2,* Hyung Joon Kim,^3,* and Eui-Cheol Shin^1,2,9,*¹Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon 34141, Republic of Korea

²Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea

³Department of Internal Medicine, Chung-Ang University Hospital, Seoul 06973, Republic of Korea

⁴Department of Surgery, College of Medicine, The Catholic University of Korea, Daejeon St. Mary’s Hospital, Daejeon 34943, Republic of Korea

⁵Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea

⁶Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea

⁷Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

⁸These authors contributed equally

⁹Lead Contact

^*Correspondence: Su-Hyung Park, Hyung Joon Kim, Eui-Cheol Shin

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.

논문정보

형식Research article
게재일2018년 01월 (BRIC 등록일 2018-01-11)
연구진국내 연구진
분야 의약학 > 면역의학

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