Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice

Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8233-8. doi: 10.1073/pnas.95.14.8233.

Abstract

To study the role of the interferon- (IFN) gammaR2 chain in IFN-gamma signaling and immune function, IFN-gammaR2-deficient mice have been generated and characterized. Cells derived from IFN-gammaR2 -/- mice are unable to activate either JAK/STAT signaling proteins or gene transcription in response to IFN-gamma. The lack of IFN-gamma responsiveness alters IFN-gamma-induced Ig class switching by B cells from these mice. In vitro cultures of T cells demonstrate that the T cells from the IFN-gammaR2 -/- mice have a defect in Th1 cell differentiation. The IFN-gammaR2 (-/-) mice also produce lower amounts of IFN-gamma in response to antigenic challenge. In addition, IFN-gammaR2 -/- mice are defective in contact hypersensitivity and are highly susceptible to infection by Listeria monocytogenes. These results demonstrate that the IFN-gammaR2 is essential for IFN-gamma-mediated immune responses in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Susceptibility / immunology
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Immune System Diseases / genetics*
  • Immune System Diseases / immunology
  • Interferon gamma Receptor
  • Interferon-gamma / immunology
  • Listeriosis / immunology
  • Mice
  • Mice, Knockout
  • Receptors, Interferon / genetics*
  • Receptors, Interferon / immunology*
  • Signal Transduction / genetics*
  • Signal Transduction / immunology*

Substances

  • Receptors, Interferon
  • Interferon-gamma