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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1996-7-18
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pubmed:abstractText |
Human natural killer (NK) cells are bone marrow (BM)-derived CD2+CD16+CD56+ large granular lymphocytes (LGL) that lack CD3 yet contain the T-cell receptor zeta-chain (zeta-TCR). NK cells provide requisite interferon-gamma (IFN-gamma) during the early stages of infection in several experimental animal models. A number of studies have shown that human CD3-CD56+ NK cells can be obtained from BM-derived CD34+ hematopoietic progenitor cells (HPCs) cultured in the presence of interleukin-2 (IL-2) and an allogeneic feeder cell layer, or IL-2 and other hematopoietic growth factors such as the c-kit ligand (KL). The failure to detect the IL-2 gene product within the BM stroma and the presence of NK cells in IL-2-deficient mice suggested that cytokines other than IL-2 may participate in NK cell differentiation from HPCs in vivo. IL-15 is a cytokine which, while lacking any sequence homology in IL-2, can activate cells via the IL-2 receptor. Here we show that human BM stromal cells express the IL-15 transcript, and supernatants from long-term BM stromal cell cultures contain IL-15 protein. In vitro, CD3-CD56+ NK cells can be obtained from 21-day cultures of CD34+ HPCs supplemented with IL-15 in the absence of IL-2, stromal cells, or other cytokines. The addition of the KL to these cultures had no effect on the differentiation of the CD3-CD56+ cytotoxic effector cells, but greatly enhanced their expansion. The majority of these cells lack CD2 and CD16, but do express zeta-TCR. Similar to NK cells found in peripheral blood, the CD2-CD16-CD56+ NK cells grown in the presence of IL-15 were found to be potent producers of IFN-gamma in response to monocyte-derived cytokines. Thus IL-15, like KL, appears to be produced by BM stromal cells. IL-15 can induce CD34+ HPCs to differentiate into CD3-CD56+ NK cells, and KL can amplify this. Therefore, IL-15 may be a physiologically relevant ligand for NK cell differentiation in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
87
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
2632-40
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8639878-Antigens, CD34,
pubmed-meshheading:8639878-Antigens, CD56,
pubmed-meshheading:8639878-Base Sequence,
pubmed-meshheading:8639878-Bone Marrow,
pubmed-meshheading:8639878-Bone Marrow Cells,
pubmed-meshheading:8639878-Cell Differentiation,
pubmed-meshheading:8639878-Cells, Cultured,
pubmed-meshheading:8639878-Hematopoietic Stem Cells,
pubmed-meshheading:8639878-Humans,
pubmed-meshheading:8639878-Immunophenotyping,
pubmed-meshheading:8639878-Interleukin-15,
pubmed-meshheading:8639878-Interleukins,
pubmed-meshheading:8639878-Killer Cells, Natural,
pubmed-meshheading:8639878-Molecular Sequence Data,
pubmed-meshheading:8639878-Stromal Cells
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pubmed:year |
1996
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pubmed:articleTitle |
Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells.
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pubmed:affiliation |
Department of Hematologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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