Fig. 10.

Proposed pathway by which TCDD pretreatment exacerbates Con A-induced liver injury. Con A activates NKT, CD4+ T-cells, and Kupffer cells, increasing production of cytokines such as IFNγ and TNF-α, as well as expression of cytolytic molecules such as Fas ligand. These mediators directly kill hepatic parenchymal cells. TCDD pretreatment increased NKT cell activation and FasL expression while also activating NK cells and increasing IFNγ production resulting in increased HPC death. Also depicted are positive feedback loops for IFNγ and TNF-α. Abbreviations: Con A, Concanavalin A; CD4+, conventional CD4+ T cells; CD69, early lymphocyte activation marker; IFNγ, interferon gamma; KC, Kupffer cells; NK, natural killer cells; NKT, natural killer T cells; TCDD, 2,3,7,8 tetrachlorodibenzo-para-dioxin; TNF-α, tumor necrosis factor alpha.