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Blood, 1 July 2007, Vol. 110, No. 1, pp. 91-98. Prepublished online as a Blood First Edition Paper on March 15, 2007; DOI 10.1182/blood-2006-11-055442. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-11-055442v1 110/1/91    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Smyth, C. M Articles by Alexander, I. E Search for Related Content PubMed PubMed Citation Articles by Smyth, C. M Articles by Alexander, I. E Related Collections Hematopoiesis and Stem Cells Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Limiting c expression differentially affects signaling via the interleukin (IL)-7 and IL-15 receptors Christine M Smyth1, Samantha L Ginn1, Claire T Deakin1, Grant J Logan1, and Ian E Alexander1,2 1 Gene Therapy Research Unit, Children's Medical Research Institute and The Children's Hospital at Westmead, Australia; and 2 Discipline of Paediatrics and Child Health, University of Sydney, Australia X-linked severe combined immunodeficiency (SCID-X1) results from mutations in the IL2RG gene, which encodes the common gamma chain (c) of the receptors for interleukin (IL)-2, 4, 7, 9, 15, and 21. Affected infants typically lack T and natural killer (NK) cells as a consequence of loss of signaling via the IL-7 receptor (IL-7R) and the IL-15R, respectively. In some infants, however, autologous NK cells are observed despite failure of T-cell ontogeny. The mechanisms by which mutations in c differentially impact T- and NK-cell ontogeny remain incompletely understood. We used SCID-X1 patient–derived EBV-transformed B cells to test the hypothesis that the IL-15R–mediated signaling is preferentially retained as c expression becomes limiting. Signal transduction via the IL-15R was readily detected in control EBV-transformed B cells, and via the IL-7R when modified to express IL-7R. Under the same experimental conditions, patient-derived EBV-transformed B cells expressing trace amounts of c proved incapable of signal transduction via the IL-7R while retaining the capacity for signal transduction via the IL-15R. An equivalent result was obtained in ED-7R cells modified to express varying levels of c. Collectively, these results confirm that signal transduction via the IL-15R, and hence NK ontogeny, is preferentially retained relative to the IL-7R as c expression becomes limiting. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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