Activating Immunity in the Liver. II. IFN-β Attenuates NK Cell-Dependent Liver Injury Triggered by Liver NKT Cell Activation

摘要: Dendritic cell (DC)-dependent activation of liver NKT cells triggered by a single i.v. injection low dose (10-100 ng/mouse) alpha-galactosyl ceramide (alphaGalCer) into mice induces injury. This response is particularly evident in HBs-tg B6 that express transgene-encoded hepatitis B surface Ag the liver. Liver injury following alphaGalCer suppressed depleted NK cells, indicating play role T cell-initiated In vitro, provide CD80/86-dependent signal to alphaGalCer-pulsed DC release IL-12 p70 stimulates IFN-gamma and cells. Adoptive transfer cell-activated nontreated, normal (immunocompetent), or immunodeficient (RAG(-/-) HBs-tg/RAG(-/-)) hosts via portal vein elicited responses situ. IFN-beta down-regulates pathogenic IL-12/IFN-gamma cytokine cascade cell/DC/NK interactions Pretreating vitro with their (but not IL-10) CD40 ligation specific (alphaGalCer-dependent) interaction down-regulated specifically activated vivo, attenuated cell-triggered induction immunopathology. study identifies interacting subsets hepatic innate immune system (and cytokines up- down-regulate these interactions) early immune-mediated pathology.