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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1996-12-17
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pubmed:abstractText |
Natural killer (NK) cells are characterized by their ability to mediate spontaneous cytotoxicity against susceptible tumor cells and infected cells. They differentiate from hematopoietic progenitor cells. Patients with X-linked severe combined immunodeficiency (SCID X1) carry mutations in the gamma c cytokine receptor gene that result in lack of both T and NK cells. To assess the role of interleukin-2 (IL-2), IL-7, and IL-15 cytokines, which share gamma c receptor subunit, in NK cell differentiation, we have studied NK cell differentiation from cord blood CD34 (+) cells in the presence of either stem cell factor (SCF), IL-2, and IL-7 or SCF and IL-15. The former cytokine combination efficiently induced CD34 (+) CD7 (+) cord blood cells to proliferate and mature into NK cells, while the latter was also able to induce NK cell differentiation from more immature CD34 (+) CD7 (-) cord blood cells. NK cells expressed CD56 and efficiently killed K562 target cells. These results show that IL-15 could play an important role in the maturation of NK cell from cord blood progenitors. Following retroviral-mediated gene transfer of gamma c into SCID X1 bone marrow progenitors, it was possible to reproduce a similar pattern of NK cell differentiation in two SCID-X1 patients with SCF + IL-2 + IL-7 and more efficiently in one of them with SCF + IL-15. These results strongly suggest that the gamma c chain transduces major signal(s) involved in NK cell differentiation from hematopoietic progenitor cells and that IL-15 interaction with gamma c is involved in this process at an earlier step than IL-2/IL-7 interactions of gamma c are. It also shows that gene transfer into hematopoietic progenitor cells could potentially restore NK cell differentiation in SCID X1 patients.
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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 |
Nov
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
88
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3901-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8916956-Antibody-Dependent Cell Cytotoxicity,
pubmed-meshheading:8916956-Bone Marrow,
pubmed-meshheading:8916956-Cell Differentiation,
pubmed-meshheading:8916956-Colony-Forming Units Assay,
pubmed-meshheading:8916956-Fetal Blood,
pubmed-meshheading:8916956-Hematopoietic Stem Cells,
pubmed-meshheading:8916956-Humans,
pubmed-meshheading:8916956-Infant,
pubmed-meshheading:8916956-Interleukin-15,
pubmed-meshheading:8916956-Interleukin-2,
pubmed-meshheading:8916956-Interleukin-7,
pubmed-meshheading:8916956-Killer Cells, Natural,
pubmed-meshheading:8916956-Male,
pubmed-meshheading:8916956-Point Mutation,
pubmed-meshheading:8916956-Polymerase Chain Reaction,
pubmed-meshheading:8916956-Proviruses,
pubmed-meshheading:8916956-Receptors, Cytokine,
pubmed-meshheading:8916956-Severe Combined Immunodeficiency,
pubmed-meshheading:8916956-Transfection
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pubmed:year |
1996
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pubmed:articleTitle |
Role of interleukin-2 (IL-2), IL-7, and IL-15 in natural killer cell differentiation from cord blood hematopoietic progenitor cells and from gamma c transduced severe combined immunodeficiency X1 bone marrow cells.
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pubmed:affiliation |
Institut National de la Santé et de la Recherche Médicale U 429, Hôpital Necker-Enfants Malades, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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