CD40 LIGAND INHIBITS FAS CD95-MEDIATED APOPTOSIS OF HUMAN BLOOD-DERIVED DENDRITIC CELLS/

Dendritic cells (DC) are considered to be the most potent antigen-pres enting cells (APC) in the immune system. In this study, we analyzed th e regulation of apoptosis of human peripheral blood-derived DC. DC wer e generated from adherent peripheral blood mononuclear cells that had been cultured for 7 days with granulocyte-macrophage colony-stimulatin g factor and interleukin-4. These cells displayed phenotypic propertie s of DC, including dendritic processes, expression of CD1a and lack of expression of CD14, and were very potent at presenting soluble antige ns to T cells. Blood-derived DC were demonstrated to express the Fas/C D95 antigen and an agonist antibody to CD95 strongly induced apoptotic cell death in these cells. Soluble trimeric CD40 ligand potently inhi bited both CD95-mediated and spontaneous apoptosis in DC. The data sug gest that interactions between members of the tumor necrosis factor fa mily of ligands expressed by T cells with their receptors on DC play a n important role in the regulation of apoptosis in DC during antigen p resentation and may, therefore, regulate the duration of T cell expans ion and cytokine production.