title: Defective expression of the interleukin-2/interleukin-15 receptor beta subunit leads to a natural killer cell-deficient form of severe combined immunodeficiency.
abstract: Development of T and natural killer (NK) cells is critically dependent on cytokine signaling, and defects in cytokine receptor complex subunits have been shown to result in severe combined immunodeficiency (SCID) syndromes in humans and in murine models. An infant boy had typical clinical features of SCID and was found to lack NK cells in his peripheral circulation. Molecular analysis did not reveal abnormalities in his gammac or JAK-3 genes, and he was investigated for defects in the interleukin-15 (IL-15) receptor complex because functional IL-15 signaling is essential for NK cell development. Expression of the IL-2R/IL-15Rbeta chain was significantly reduced in the patient's peripheral blood mononuclear cells (PBMCs) by immunoblot, flow cytometry, and Northern blot analysis. Furthermore, IL-2 stimulation of PBMCs showed only minimal tyrosine phosphorylation of JAK-3. These data demonstrate that defects in IL-2R/1L-15Rbeta expression can lead to a unique NK-deficient SCID immunophenotype. (Blood. 2001;98:877-879)
authors.affiliation: Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford St., London WC1N 1EH, UK.
authors.forename: K C
authors.initials: KC
authors.lastname: Gilmour
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Cranston
authors.forename: E G
authors.initials: EG
authors.lastname: Davies
authors.forename: C
authors.initials: C
authors.lastname: Kinnon
authors.forename: H B
authors.initials: HB
authors.lastname: Gaspar
mesh_terms: D005091:Exons / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D053646:Interleukin-2 Receptor beta Subunit; D007694:Killer Cells, Natural / Q000473:pathology*; D008297:Male; D018807:Polymorphism, Single-Stranded Conformational; D021122:Protein Subunits; D018123:Receptors, Interleukin / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D017422:Sequence Analysis, DNA; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C508024:IL15RA protein, human; C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D021122:Protein Subunits; D018123:Receptors, Interleukin; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2