Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients

Science. 1998 May 29;280(5368):1435-8. doi: 10.1126/science.280.5368.1435.


Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (TH1) responses and interferon-gamma (IFN-gamma) production. IL-12 binds to high-affinity beta1/beta2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and Salmonella infections were found to lack IL-12Rbeta1 chain expression. Their cells were deficient in IL-12R signaling and IFN-gamma production, and their remaining T cell responses were independent of endogenous IL-12. IL-12Rbeta1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rbeta1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child, Preschool
  • Codon, Terminator
  • Disease Susceptibility
  • Female
  • Frameshift Mutation
  • Genes, Recessive
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / immunology*
  • Interleukin-12 / metabolism
  • Lymphocyte Activation
  • Mutation
  • Mycobacterium avium-intracellulare Infection / immunology*
  • Mycobacterium bovis*
  • Receptors, Interferon / metabolism
  • Receptors, Interleukin / deficiency
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-12
  • Salmonella Infections / immunology*
  • Sequence Deletion
  • T-Lymphocytes / immunology
  • Tuberculosis / immunology*


  • Codon, Terminator
  • IL12RB1 protein, human
  • IL12RB2 protein, human
  • Receptors, Interferon
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • interferon gamma receptor
  • Interleukin-12
  • Interferon-gamma