CD40 ligand inhibits Fas/CD95‐mediated apoptosis of human blood‐derived dendritic cells

Abstract Dendritic cells (DC) are considered to be the most potent antigen‐presenting cells (APC) in the immune system. In this study, we analyzed the regulation of apoptosis of human peripheral blood‐derived DC. DC were generated from adherent peripheral blood mononuclear cells that had been cultured for 7 days with granulocyte‐macrophage colony‐stimulating factor and interleukin‐4. These cells displayed phenotypic properties of DC, including dendritic processes, expression of CD1a and lack of expression of CD14, and were very potent at presenting soluble antigens to T cells. Blood‐derived DC were demonstrated to express the Fas/CD95 antigen and an agonist antibody to CD95 strongly induced apoptotic cell death in these cells. Soluble trimeric CD40 ligand potently inhibited both CD95‐mediated and spontaneous apoptosis in DC. The data suggest that interactions between members of the tumor necrosis factor family of ligands expressed by T cells with their receptors on DC play an important role in the regulation of apoptosis in DC during antigen presentation and may, therefore, regulate the duration of T cell expansion and cytokine production.