Periportal and sinusoidal liver dendritic cells suppressing T helper type 1-mediated hepatitis

Abstract

Background: Recently, we found that portal vein tolerance is associated with generation of Th2 cells and apoptosis of Th1 cells in the liver, which is regulated by antigen (Ag)-presenting dendritic cells (DCs) in the periportal area and sinusoids.

Aim: In this study, we tested whether the periportal and sinusoidal DCs, which were loaded with an Ag in vivo, can inhibit liver injury caused by Th1 cells activated by the Ag administered systemically.

Methods: Ag-specific hepatitis model was created by adoptively transferring ovalbumin (OVA)-specific CD4(+) T cells to BALB/c mice and venous injection of OVA-containing liposomes. Liver CD11c(+) cells obtained from mice fed OVA were then transferred into these mice.

Results: The transfer of liver CD11c(+) cells from OVA-fed mice completely inhibited hepatic injury, which was associated with apoptosis of OVA-specific CD4(+) T cells and emergence of Th2 cells in the liver. Transfer of CD11c(+) cells and subcutaneous OVA challenge led to enhancement of OVA-specific IgE Ab as well as Th2 cytokine responses in the recipient mice.

Conclusions: Periportal and sinusoidal DCs loaded with an Ag in the portal vein can induce Th2 response in the liver and prevent hepatic injury caused by Th1 cells.