Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum

Cristina Bergamaschi, Jenifer Bear, Margherita Rosati, Rachel Kelly Beach, Candido Alicea, Raymond Sowder, Elena Chertova, Steven A. Rosenberg, Barbara K. Felber, George N. Pavlakis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)e1-e8
JournalBlood
Volume120
Issue number1
DOIs
StatePublished - Jul 5 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Bergamaschi, C., Bear, J., Rosati, M., Beach, R. K., Alicea, C., Sowder, R., Chertova, E., Rosenberg, S. A., Felber, B. K., & Pavlakis, G. N. (2012). Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum. Blood, 120(1), e1-e8. https://doi.org/10.1182/blood-2011-10-384362