Abnormal regulation of interferon-γ, interleukin-12, and tumor necrosis factor-α in human interferon-γ receptor 1 deficiency

Steven M. Holland, Susan E. Dorman, Annette Kwon, Ian F. Pitha-Rowe, David M. Frucht, Susan M. Gerstberger, Gary J. Noel, Per Vesterhus, Margaret R. Brown, Thomas A. Fleisher

Research output: Contribution to journalArticle

Abstract

Mycobacterial infections are critically controlled by interferon-γ (IFN-γ) and the cellular responses it elaborates, as shown by patients with mutations in the IFN-γ receptor ligand-binding chain (IFN-γR1) who have disseminated nontuberculous mycobacterial infections. The immunologic sequelae of IFN-γR1 deficiency were characterized in 2 unrelated patients from the Indian subcontinent with novel homozygous recessive IFN-γR1 mutations. In vitro, these patients' peripheral blood mononuclear cells produced 10% of normal IFN-γ and interleukin-12 (IL-12) in response to phytohemagglutinin (PHA) but normal amounts of IFN-γ in response to PHA plus IL-12. Tumor necrosis factor-α (TNF-α) production was normal in response to endotoxin and to PHA but was not augmented by the addition of IFN-γ. An abnormal phenotype was not found in heterozygous patient relatives. These patients demonstrate the critical role that the IFN-γ receptor plays in the regulation of IFN-γ, IL-12, and TNF-α.

Original languageEnglish (US)
Pages (from-to)1095-1104
Number of pages10
JournalJournal of Infectious Diseases
Volume178
Issue number4
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Holland, S. M., Dorman, S. E., Kwon, A., Pitha-Rowe, I. F., Frucht, D. M., Gerstberger, S. M., Noel, G. J., Vesterhus, P., Brown, M. R., & Fleisher, T. A. (1998). Abnormal regulation of interferon-γ, interleukin-12, and tumor necrosis factor-α in human interferon-γ receptor 1 deficiency. Journal of Infectious Diseases, 178(4), 1095-1104. https://doi.org/10.1086/515670