Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum
Open Access
- 5 July 2012
- journal article
- Published by American Society of Hematology in Blood
- Vol. 120 (1), e1-e8
- https://doi.org/10.1182/blood-2011-10-384362
Abstract
IL-15 is an important cytokine for the function of the immune system, but the form(s) of IL-15 produced in the human body are not fully characterized. Coexpression of the single-chain IL-15 and the IL-15 receptor alpha (IL-15Rα) in the same cell allows for efficient production, surface display, and eventual cleavage and secretion of the bioactive IL-15/IL-15Rα heterodimer in vivo, whereas the single-chain IL-15 is poorly secreted and unstable. This observation led to the hypothesis that IL-15 is produced and secreted only as a heterodimer with IL-15Rα. We purified human IL-15/IL-15Rα complexes from overproducing human cell lines and developed an ELISA specifically measuring the heterodimeric form of IL-15. Analysis of sera from melanoma patients after lymphodepletion revealed the presence of circulating IL-15/IL-15Rα complexes in amounts similar to the total IL-15 quantified by a commercial IL-15 ELISA that detects both the single-chain and the heterodimeric forms of the cytokine. Therefore, in lymphodepleted cancer patients, the serum IL-15 is exclusively present in its heterodimeric form. Analysis of the form of IL-15 present in either normal or lymphodepleted mice agrees with the human data. These results have important implications for development of assays and materials for clinical applications of IL-15.This publication has 48 references indexed in Scilit:
- Tumor Necrosis Factor Signaling Requires iRhom2 to Promote Trafficking and Activation of TACEScience, 2012
- IL-15 transpresentation promotes both human T-cell reconstitution and T-cell–dependent antibody responses in vivoProceedings of the National Academy of Sciences of the United States of America, 2011
- IL-15 trans-presentation promotes human NK cell development and differentiation in vivoThe Journal of Experimental Medicine, 2008
- How a Cytokine Is Chaperoned through the Secretory Pathway by Complexing with Its Own Receptor: Lessons from Interleukin-15 (IL-15)/IL-15 Receptor αMolecular and Cellular Biology, 2008
- IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentationThe Journal of Experimental Medicine, 2008
- Dendritic Cells Prime Natural Killer Cells by trans-Presenting Interleukin 15Immunity, 2007
- The IL-15/IL-15Rα on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine designNature Reviews Immunology, 2006
- Converting IL-15 to a superagonist by binding to soluble IL-15RαProceedings of the National Academy of Sciences of the United States of America, 2006
- IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primatesJCI Insight, 2006