Hepatic T cells and liver tolerance

Top Cited Papers
Publisher Website
Google Scholar
Abstract
The liver is perfused by a mixture of arterial blood and blood from the intestines carrying food antigens. In the liver, blood flows through sinusoids lined with a distinctive endothelium that lacks a basement membrane and is perforated by clusters of holes (fenestrations). The sinusoidal spaces contain a large macrophage population, known as Kupffer cells. The liver lymphocytes are enriched in natural killer (NK) cells, natural killer T (NKT) cells and apoptotic T cells, many of which are derived from circulating CD8+ T cells. Dendritic-cell precursors traffic through the liver, but resident liver cells, including Kupffer cells, liver sinusoidal endothelial cells and hepatocytes, might be involved in antigen presentation also. Presentation of antigen in the liver can result in either T-cell priming or T-cell tolerance. The liver can impose tolerance by T-cell apoptosis (mainly of CD8+ T cells) or by the induction of a regulatory phenotype (mainly of CD4+ T cells). An important pathogen of humans, hepatitis C virus, has evolved many methods of immune evasion. These include classic escape mutations, mutations that create antagonistic peptides, functional inactivation of T cells (known as 'stunning') and inactivation of NK cells. Hepatocytes express CD95 (FAS), a death receptor that is upregulated during inflammation. This predisposes the liver to damage whenever FAS-ligand-expressing lymphocytes are present.