Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-12-17
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3901-9
pubmed:dateRevised
2006-11-15
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
pubmed:year
1996
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.
pubmed:affiliation
Institut National de la Santé et de la Recherche Médicale U 429, Hôpital Necker-Enfants Malades, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't