Bergamaschi, Cristina;
Bear, Jenifer;
Rosati, Margherita;
Beach, Rachel Kelly;
Alicea, Candido;
Sowder, Raymond;
Chertova, Elena;
Rosenberg, Steven A.;
Felber, Barbara K.;
Pavlakis, George N.
Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum
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Medientyp:
E-Artikel
Titel:
Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum
Beteiligte:
Bergamaschi, Cristina;
Bear, Jenifer;
Rosati, Margherita;
Beach, Rachel Kelly;
Alicea, Candido;
Sowder, Raymond;
Chertova, Elena;
Rosenberg, Steven A.;
Felber, Barbara K.;
Pavlakis, George N.
Erschienen:
American Society of Hematology, 2012
Erschienen in:
Blood, 120 (2012) 1, Seite e1-e8
Sprache:
Englisch
DOI:
10.1182/blood-2011-10-384362
ISSN:
0006-4971;
1528-0020
Entstehung:
Anmerkungen:
Beschreibung:
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.