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

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 HwangWon Kim, Su Hyung Park, Hyung Joon Kim, Eui Cheol Shin

Research output: Contribution to journalArticle

36 Citations (Scopus)

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. During acute hepatitis A, hepatitis A virus (HAV)-infected cells produce IL-15 that induces TCR-independent bystander activation of non-HAV-specific memory CD8 + T cells. These CD8 + T cells exert innate-like cytotoxicity triggered by NKG2D and NKp30 without TCR engagement. The severity of liver injury is associated with activation and innate-like cytotoxicity of non-HAV-specific CD8 + T cells, but not the activation of HAV-specific T cells. Thus, IL-15-induced bystander-activated CD8 + T cells are implicated in host injury during acute viral infection.

Original languageEnglish
Pages (from-to)161-173.e5
JournalImmunity
Volume48
Issue number1
DOIs
Publication statusPublished - 2018 Jan 16
Externally publishedYes

Keywords

  • CD8 T cells
  • IL-15
  • NKG2D
  • bystander activation
  • host injury
  • immunopathogenesis
  • viral hepatitis
  • virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Kim, J., Chang, D. Y., Lee, H. W., Lee, H., Kim, J. H., Sung, P. S., Kim, K. H., Hong, S. H., Kang, W., Lee, J., Shin, S. Y., Yu, H. T., You, S., Choi, Y. S., Oh, I., Lee, D. H., Lee, D. H., Jung, M. K., Suh, K. S., ... Shin, E. C. (2018). Innate-like Cytotoxic Function of Bystander-Activated CD8 + T Cells Is Associated with Liver Injury in Acute Hepatitis A Immunity, 48(1), 161-173.e5. https://doi.org/10.1016/j.immuni.2017.11.025