4-1BB-ligand is regulated on human dendritic cells and induces the production of IL-12

Co-stimulation via 4-1BB and its ligand 4-1BB ligand (4-1BB-L) plays an important role in cytotoxic and pro-inflammatory immune responses. 4-1BB-L is generally described on activated antigen-presenting cells but there is limited information on its expression and function in human dendritic cells (DC). We herein compared purified CD1a+CD14- DC issued from monocytes or from hematopoietic progenitor cells (HPC). These DC expressed 4-1BB-L mRNA transcripts with highest cell surface levels on HPC-derived DC cultured with IL-1. Pro-inflammatory activation, particularly CD40 ligand+IL-1, up-regulated 4-1BB-L on DC. We confirmed reverse signaling via 4-1BB-L as immobilized 4-1BB in conjunction with CD40-L, enhanced IL-12beta mRNA and the secretion of IL-12 p70 in various APC, including monocytes. Altogether, DC may differ in T cell co-stimulation properties due to variable and regulated levels of 4-1BB-L. Data illustrate reciprocal stimulations between T cells and APC via up-regulated receptor/ligands and production of key cytokines that consolidate cellular immune responses.