The disabled dendritic cell

Dendritic cells are important antigen-presenting cells of the immune system that induce and modulate immune responses. They interact with T and B lymp hocytes as well as with natural killer cells to promote activation and diff erentiation of these cells. Dendritic cells generated in vitro from monocyt es by use of the cytokines GM-CSF and IL-4 are increasingly used clinically to enhance antitumor immunity in cancer patients. However, recent studies revealed that the functional repertoire of monocyte-derived dendritic cells may be incomplete. important functions of monocyte-derived dendritic cells such as migration or the ability to induce natural killer cell activation or type 2 T helper cell differentiation appear to be impaired. We propose t hat ah these deficiencies relate to a single biochemical deficiency of mono cyte derived dendritic cells. IL-4, which is used to generate monocyte-deri ved dendritic cells, suppresses phospholipase A2, the enzyme that liberates arachidonic acid from membrane phospholipids and contributes to the synthe sis of platelet-activating factor. Monocyte-derived dendritic cells must th erefore fail to generate platelet-activating factor as well as arachidonic acid derivatives such as prostaglandins, leukotrienes, and lipoxins, collec tively referred to as eicosanoids, Since eicosanoids and platelet-activatin g factor are known to play an important role in processes such as leukocyte migration, natural killer cell activation, and type 2 T helper cell differ entiation, the deficiency in eicosanoid and platelet-activating factor bios ynthesis may be responsible for the observed handicaps of monocyte-derived dendritic cells.