Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency

Nat Genet. 1998 Dec;20(4):394-7. doi: 10.1038/3877.


Severe combined immunodeficiency (SCID) is caused by multiple genetic defects. The most common form of SCID, X-linked SCID (XSCID), results from mutations in IL2RG (ref. 4), which encodes the common cytokine receptor gamma chain (gamma(c)) that is shared by the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. In XSCID and SCID resulting from mutations in JAK3, which encodes a Janus family tyrosine kinase that couples to gamma(c) and is required for gamma(c)-dependent signalling, T- and natural killer (NK)-cells are decreased but B-cell numbers are normal (T(-)B(+)NK(-)SCID). Some SCID patients lack T cells but retain NK cells. Given diminished T-cell development in Il7- or Il7r-deficient mice and that Il/7r-deficient mice have NK cells, we hypothesized that T(-)B(+)NK(+) SCID might result from defective IL-7 signalling, although apparent differences in the role of the IL-7/IL-7R pathway in humans and mice in T-cell and B-cell development have been suggested. We now demonstrate that defective IL7R expression causes T(-)B(+)NK(+) SCID, indicating that the T-cell, but not the NK-cell, defect in XSCID results from inactivation of IL-7Ralpha signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Base Sequence
  • DNA Primers
  • Humans
  • Infant
  • Infant, Newborn
  • Killer Cells, Natural / immunology
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Polymerase Chain Reaction
  • Receptors, Interleukin-7 / genetics*
  • Receptors, Interleukin-7 / metabolism
  • Severe Combined Immunodeficiency / genetics*
  • Signal Transduction / genetics
  • T-Lymphocytes / immunology


  • DNA Primers
  • Receptors, Interleukin-7

Associated data

  • GENBANK/AF043123
  • GENBANK/AF043124
  • GENBANK/AF043125
  • GENBANK/AF043126
  • GENBANK/AF043127
  • GENBANK/AF043128
  • GENBANK/AF043129