In vitro and in vivo protection of stellate cells from apoptosis by leptin.

Hepatic fibrogenesis is reduced in the absence of leptin. We hypothesized that leptin protects hepatic stellate cells (HSCs) from apoptosis and tested this in in vitro and in vivo systems. (i) Fas ligand (fas-L)-mediated apoptosis was induced in vitro in activated HSCs in the absence and presence of leptin.

Blocking intrahepatic deletion of activated CD8+ T cells by an altered peptide ligand.

Background: Activated CD8(+) T cells are retained by the healthy liver where the majority undergo apoptosis. The intrahepatic apoptosis of activated CD8(+) T cells is enhanced by the presence of SIINFEKL peptide. It is of great interest to identify strategies for maintaining intrahepatic T cell number and function in the presence of SIINFEKL peptides.

Kupffer cells required for high affinity peptide-induced deletion, not retention, of activated CD8+ T cells by mouse liver.

The immune response to foreign antigens in the liver is often suboptimal and this is clinically relevant in chronic persistence of hepatotropic viruses. In chronic infection with the hepatitis C virus, activated CD8+ T cells specific for viral epitopes are present in the peripheral blood and the liver, yet viral clearance is unusual. To define the fate of activated CD8+ entering the liver, we developed a mouse model of portal vein injection of activated CD8+ T cells in vivo.