T cell-mediated host injury

Recently, we studied mechanisms of immunopathologic host injury that occurs during acute hepatitis A caused by hepatitis A virus (HAV) infection and published the results (Kim J et al. Immunity 48:161, 2018; Choi YS et al. Gastroenterology 154:1047, 2018). During acute hepatitis A, over-produced IL-15 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 (Kim J et al. Immunity 48:161, 2018). In addition, we found that CD4+CD25+FoxP3+ regulatory T (Treg) cells paradoxically produce TNF-a during acute hepatitis A in an RORgt-dependent manner (Choi YS et al. Gastroenterology 154:1047, 2018). Currently, we are studying immunopathologic roles of bystander-activated CD8+ T cells and TNF-producing Treg cells in other human viral diseases and chronic inflammatory diseases.