Impaired function of dendritic cells translocating the liver sinusoids: A veto effect contributing to intrahepatic tolerance?

Abstract

Due to its unique architecture and conditions of blood flow, the liver is acknowledged as an immunologically unusual organ associated with primary activation of naïve T cells and the induction of tolerance. Several mechanisms have been proposed to be involved in this process. Most suggest that naïve T cells activated in situ in the hepatic sinusoids are deleted or silenced following activation by liver cells acting as antigen presenting cells. Hepatocytes, liver sinusoidal endothelial cells and bone marrow-derived cells (including Kupffer cells and DC) have been shown to support primary activation in situ and play some role in tolerance induction. Although most liver DC have been described to be immature and located in sites inaccessible to naïve T cells, some blood-borne DC have been shown to translocate via the sinusoids where naïve T cells recirculate. Thus, the presence of mature DC with potential immunogenicity in the sinusoids might give contradictory signals to the naïve T cells activated within this organ. In this issue of the European Journal of Immunology, liver sinusoidal endothelial cells are shown to impair the DC ability to induce the proliferation of naïve T cells in vitro via an unknown mechanism. Although these findings need to be confirmed in a physiological setting, regulation of the function of DC translocating the sinusoids might represent a new mechanism contributing to T cell tolerance in the liver. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.