期刊
BLOOD
卷 120, 期 1, 页码 E1-E8出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-10-384362
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资金
- National Cancer Institute
- National Institutes of Health [HHSN261200800001E]
- Research Program of the Center for Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI)
- NIH
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-15R alpha) in the same cell allows for efficient production, surface display, and eventual cleavage and secretion of the bioactive IL-15/IL-15R alpha 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-15R alpha. We purified human IL-15/IL-15R alpha 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-15R alpha 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. (Blood. 2012;120(1):e1-e8)
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