Immune regulatory activity of liver-derived dendritic cells generated in vivo.

Hepatic tolerance is demonstrated by spontaneous acceptance of liver allografts in mice. Hepatic dendritic cells (DC) play a crucial role in determining immunity or tolerance. In this study, we adopted an approach to transfect gene(s) into the mouse liver by tail-vein injection of plasmid-carrying genes. Transfection with GM-CSF expanded liver CD11c+ myeloid DC (LMDC), while liver B220+CD11c- lymphoid DC (LLDC) were expanded after transfection of IL-3 and CD40L. Flow analysis revealed that these liver DC subsets were phenotypically mature following overnight culture. However, in contrast to LMDC, LLDC induced hyporesponsiveness in allogeneic T-cells, with suppressed secretion of both IL-2 and IFN-gamma, and prolonged cardiac allograft survival. This immune regulatory DC population in the liver may play a role in modulating T-cell immunity in the liver.