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Kim, Jihye; Chang, Dong-Yeop; Lee, Hyun Woong; Lee, Hoyoung; Kim, Jong Hoon; Sung, Pil Soo; Kim, Kyung Hwan; Hong, Seon-Hui; Kang, Wonseok; Lee, Jino; Shin, So Youn; Yu, Hee Tae; You, Sooseong; Choi, Yoon Seok; Oh, Insoo; Lee, Dong Ho; Lee, Dong Hyeon; Jung, Min Kyung; Suh, Kyung-Suk; Hwang, Shin; Kim, Won; Park, Su-Hyung; Kim, Hyung Joon; Shin, Eui-Cheol
Immunity (Cambridge, Mass.), 01/2018, Letnik: 48, Številka: 1Journal Article
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. Display omitted •During acute hepatitis A (AHA), non-HAV-specific memory CD8+ T cells are activated•Non-HAV-specific CD8+ T cells are activated by IL-15 produced by HAV-infected cells•CD8+ T cells of AHA patients exert TCR-independent, innate-like cytotoxicity•Innate-like cytotoxicity of CD8+ T cells is associated with liver injury in AHA 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.
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