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 lymphocytes as well as with natural killer cells to promote activation and differentiation of these cells. Dendritic cells generated in vitro from monocytes 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 that all these deficiencies relate to a single biochemical deficiency of monocyte‐derived dendritic cells. IL‐4, which is used to generate monocyte‐derived dendritic cells, suppresses phospholipase A2, the enzyme that liberates arachidonic acid from membrane phospholipids and contributes to the synthesis of platelet‐activating factor. Monocyte‐derived dendritic cells must therefore fail to generate platelet‐activating factor as well as arachidonic acid derivatives such as prostaglandins, leukotrienes, and lipoxins, collectively referred to as eicosanoids. Since eicosanoids and platelet‐activating factor are known to play an important role in processes such as leukocyte migration, natural killer cell activation, and type 2 T helper cell differentiation, the deficiency in eicosanoid and platelet‐activating factor biosynthesis may be responsible for the observed handicaps of monocyte‐derived dendritic cells.—Thumher, M., Zelle‐Rieser, C., Ramoner, R., Bartsch, G., Höltl, L. The disabled dendritic cell. FASEB J. 15, 1054–1061 (2001)