title: 4-1BB-ligand is regulated on human dendritic cells and induces the production of IL-12.
abstract: 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.
authors.affiliation: Department of Immunology and Microbiology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Laderach
authors.forename: Amy
authors.initials: A
authors.lastname: Wesa
authors.forename: Anne
authors.initials: A
authors.lastname: Galy
mesh_terms: D053330:4-1BB Ligand; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D008024:Ligands; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D053330:4-1BB Ligand; D016207:Cytokines; D008024:Ligands; C505974:TNFSF9 protein, human; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12