Submitted November 1, 2006
Accepted March 7, 2007
Limiting 
c expression differentially affects signaling via the interleukin (IL)-7 and IL-15 receptors
Christine M Smyth, Samantha L Ginn, Claire T Deakin, Grant J Logan, and Ian E Alexander*
Gene Therapy Research Unit, Children's Medical Research Institute and The Children's Hospital at Westmead, Westmead, Australia
Discipline of Paediatrics and Child Health, University of Sydney, Sydney, Australia
* Corresponding author; email: iana{at}chw.edu.au.
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 IL-2, 4, 7, 9, 15 and 21. Affected infants typically lack T and NK cells as a consequence of loss of signaling via the IL-7R and 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 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.
