title: Abnormal regulation of interferon-gamma, interleukin-12, and tumor necrosis factor-alpha in human interferon-gamma receptor 1 deficiency.
abstract: Mycobacterial infections are critically controlled by interferon-gamma (IFN-gamma) and the cellular responses it elaborates, as shown by patients with mutations in the IFN-gamma receptor ligand-binding chain (IFN-gamma R1) who have disseminated nontuberculous mycobacterial infections. The immunologic sequelae of IFN-gamma R1 deficiency were characterized in 2 unrelated patients from the Indian subcontinent with novel homozygous recessive IFN-gamma R1 mutations. In vitro, these patients' peripheral blood mononuclear cells produced 10% of normal IFN-gamma and interleukin-12 (IL-12) in response to phytohemagglutinin (PHA) but normal amounts of IFN-gamma in response to PHA plus IL-12. Tumor necrosis factor-alpha (TNF-alpha) production was normal in response to endotoxin and to PHA but was not augmented by the addition of IFN-gamma. An abnormal phenotype was not found in heterozygous patient relatives. These patients demonstrate the critical role that the IFN-gamma receptor plays in the regulation of IFN-gamma, IL-12, and TNF-alpha.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. smh@nih.gov
authors.forename: S M
authors.initials: SM
authors.lastname: Holland
authors.forename: S E
authors.initials: SE
authors.lastname: Dorman
authors.forename: A
authors.initials: A
authors.lastname: Kwon
authors.forename: I F
authors.initials: IF
authors.lastname: Pitha-Rowe
authors.forename: D M
authors.initials: DM
authors.lastname: Frucht
authors.forename: S M
authors.initials: SM
authors.lastname: Gerstberger
authors.forename: G J
authors.initials: GJ
authors.lastname: Noel
authors.forename: P
authors.initials: P
authors.lastname: Vesterhus
authors.forename: M R
authors.initials: MR
authors.lastname: Brown
authors.forename: T A
authors.initials: TA
authors.lastname: Fleisher
mesh_terms: D000595:Amino Acid Sequence; D002675:Child, Preschool; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D015269:Mycobacterium avium Complex / Q000276:immunology*; D010154:Pakistan / Q000208:ethnology; D010375:Pedigree; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D018664:Interleukin-12; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor