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

被引：138
作者：
Bergamaschi, Cristina
Bear, Jenifer [2 ]
Rosati, Margherita
Beach, Rachel Kelly [2 ]
Alicea, Candido [2 ]
Sowder, Raymond [3 ]
Chertova, Elena [3 ]
Rosenberg, Steven A. [4 ]
Felber, Barbara K. [2 ]
Pavlakis, George N. [1 ]
机构：
[1] FNLCR, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA
[2] FNLCR, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA
[3] FNLCR, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA
[4] NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA
来源：
BLOOD | 2012年 / 120卷 / 01期
基金：
美国国家卫生研究院;
关键词：
NATURAL-KILLER-CELLS; TRANS-PRESENTATION; RECEPTOR-ALPHA; T-CELLS; BETA-CHAIN; EXPRESSION; INTERLEUKIN-15; PROLIFERATION; CYTOKINE; NK;
D O I：
10.1182/blood-2011-10-384362
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
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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页码：E1 / E8
页数：8
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