BACKGROUND/AIMS: T cell immune responses play key roles in the pathogenesis of viral hepatitis, and innate immunity is known to be also activated during this process, however, the effects of innate immunity activation on T cell-mediated hepatitis remain obscure. Here we examined the effect of the activation of NK cells induced by toll-like receptor 3 (TLR3) ligand, polyinosinic-polycytidylic acid (poly I:C), on concanavalin A (Con A)-induced T cell-mediated liver injury. METHODS: Mice received nontoxic intraperitoneal poly I:C injection before Con A intravenous administration. The liver injury was examined by measuring serum transaminase and pathology, and the function of hepatic lymphocytes was detected by FACS analysis. RESULTS: Poly I:C pretreatment protected against T cell-mediated hepatitis, as evidenced by decreased mortality, hepatic necrosis, serum transaminase levels and inflammatory cytokines (IL-4, IFN-gamma). The protective effect of poly I:C was diminished in NK-depleted mice, which could be partially restored by adoptive transfer of NK cells. Administration of poly I:C caused NKT and T cell apoptosis via enhancing expression of Fas protein on these cells and expression of Fas ligand on NK cells. CONCLUSIONS: These findings suggest that activation of NK cells by poly I:C prevents Con A-induced T cell-hepatitis via downregulation of T/NKT cells and subsequent reduction of inflammatory cytokines.
BACKGROUND/AIMS: T cell immune responses play key roles in the pathogenesis of viral hepatitis, and innate immunity is known to be also activated during this process, however, the effects of innate immunity activation on T cell-mediated hepatitis remain obscure. Here we examined the effect of the activation of NK cells induced by toll-like receptor 3 (TLR3) ligand, polyinosinic-polycytidylic acid (poly I:C), on concanavalin A (Con A)-induced T cell-mediated liver injury. METHODS:Mice received nontoxic intraperitoneal poly I:C injection before Con A intravenous administration. The liver injury was examined by measuring serum transaminase and pathology, and the function of hepatic lymphocytes was detected by FACS analysis. RESULTS:Poly I:C pretreatment protected against T cell-mediated hepatitis, as evidenced by decreased mortality, hepatic necrosis, serum transaminase levels and inflammatory cytokines (IL-4, IFN-gamma). The protective effect of poly I:C was diminished in NK-depleted mice, which could be partially restored by adoptive transfer of NK cells. Administration of poly I:C caused NKT and T cell apoptosis via enhancing expression of Fas protein on these cells and expression of Fas ligand on NK cells. CONCLUSIONS: These findings suggest that activation of NK cells by poly I:C prevents Con A-induced T cell-hepatitis via downregulation of T/NKT cells and subsequent reduction of inflammatory cytokines.
Authors: Linrong Lu; Koichi Ikizawa; Dan Hu; Miriam B F Werneck; Kai W Wucherpfennig; Harvey Cantor Journal: Immunity Date: 2007-05 Impact factor: 31.745
Authors: Marla Karine Amarante; Karen Brajão de Oliveira; Roberta Losi Guembarovski; Ana Cristina da Silva do Amaral Herrera; Alda Losi Guembarovski; Walter Jorge Sobrinho; Julio Cesar Voltarelli; Maria Angelica Ehara Watanabe Journal: Mol Biol Rep Date: 2012-10-11 Impact factor: 2.316
Authors: Y M Ambrosini; G-X Yang; W Zhang; M Tsuda; S Shu; K Tsuneyama; P S C Leung; A A Ansari; R L Coppel; M E Gershwin Journal: Clin Exp Immunol Date: 2011-10 Impact factor: 4.330