Journal
CELLULAR IMMUNOLOGY
Volume 226, Issue 1, Pages 37-44Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2003.11.003
Keywords
antigen-presenting cells; dendritic cells; human; 4-1BB ligand; IL-12; immune response
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Funding
- NCI NIH HHS [R01 CA82884-03] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA082884] Funding Source: NIH RePORTER
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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 1L-1. Pro-inflammatory activation, particularly CD40 ligand+1L-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. (C) 2003 Elsevier Inc. All rights reserved.
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