Activating immunity in the liver. I. Liver dendritic cells (but not hepatocytes) are potent activators of IFN-gamma release by liver NKT cells

A prominent subset of the hepatic innate immune system is alpha -galactosyl ceramide (alpha GalCer)-reactive, (CD4(+) and CD4(-)CD8(-)) Mid-restricted NKT cells. We investigated in C57BL/6 (B6) mice which hepatic cell type sti mulates hepatic NKT cell activation. Surface expression of CD1d but not CD4 0, CD80, or CD86 costimulator molecules was detected in hepatocytes. Pulsed in vitro or in vivo with alpha GalCer, hepatocytes triggered IL-4 release by liver NKT cells but required exogenous IL-12 to trigger IFN-gamma releas e by NKT cells. Liver dendritic cells (DC) isolated from nontreated mice sh owed low surface expression of MHC, CD1d, and CD40, CD80, or CD86 costimula tor molecules that were strikingly up-regulated after aGalCer injection. Al though liver CD11c(+) DC displayed lower CD1d surface expression than hepat ocytes, they were potent stimulators of IFN-gamma and IL-4 release by liver NKT when pulsed with alpha GalCer in vitro or in vivo. Liver DC are thus p otent stimulators of proinflammatory cytokine release by NKT cells, are act ivated themselves in the process of NKT cell activation, and express an act ivated phenotype after the NKT cell population is eliminated following alph a GalCer stimulation.