Publication Date:
1998-06-20
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Jong, R -- Altare, F -- Haagen, I A -- Elferink, D G -- Boer, T -- van Breda Vriesman, P J -- Kabel, P J -- Draaisma, J M -- van Dissel, J T -- Kroon, F P -- Casanova, J L -- Ottenhoff, T H -- New York, N.Y. -- Science. 1998 May 29;280(5368):1435-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunohematology and Bloodbank, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9603733" target="_blank"〉PubMed〈/a〉
Keywords:
Adult
;
Child, Preschool
;
Codon, Terminator
;
Disease Susceptibility
;
Female
;
Frameshift Mutation
;
Genes, Recessive
;
Humans
;
Interferon-gamma/biosynthesis
;
Interleukin-12/*immunology/metabolism
;
Lymphocyte Activation
;
Mutation
;
Mycobacterium avium-intracellulare Infection/*immunology
;
*Mycobacterium bovis
;
Receptors, Interferon/metabolism
;
Receptors, Interleukin/deficiency/*genetics/metabolism
;
Receptors, Interleukin-12
;
Salmonella Infections/*immunology
;
Sequence Deletion
;
T-Lymphocytes/immunology
;
Tuberculosis/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
