Immunomodulation after Liver Transplantation: a role for dentritic cells

The liver is the largest organ in the body with essential metabolic activities. In the liver large amounts of oxygenated blood carried by the hepatic artery are used to mobilize energy from dietary components. Toxic compounds, derived from food are transported from the bowel via the portal vein and detoxifi ed in the liver. In order to avoid unwarranted responses to harmless dietary proteins and components of the commensal intestinal fl ora, tight control of the local immune response in the liver is mandatory. However as a consequence the liver is a target for chronic viral and parasitic infections and metastasis of malignant diseases develop relatively easily in the liver. To meet these specifi c requirements, the repertoire of immune cells present in the liver differs dramatically from those in other non-lymphoid tissues of the body, and is considered to play a specialized role in hepatic immune responses. The liver hosts various unique resident cell types with immune potential, such as a lymphoid population selectively enriched for CD8+ T cells, NK cells and NKT cells, and cells with accessory immunologic functions such as dendritic cells (DC), Kupffer cells, sinusoidal endothelial cells and biliary epithelial cells. It is hypothesized that DC, the most potent antigen presenting cells, are the key players in maintaining the fi ne balance between immune responsiveness and unresponsiveness in the liver. Under normal circumstances, most peripheral tissues, such as the liver, contain immature DC, whose function is uptake and processing of antigen. Under steady state conditions there is a continuous migration of DC towards the draining lymph nodes (LN) and this process is accelerated upon antigenic stimulation. During this migration DC mature and acquire a strong T cell stimulatory capacity.

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