Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice.
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.
Lu
B
B
Integrated Program of Molecular, Cellular, and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Ebensperger
C
C
Dembic
Z
Z
Wang
Y
Y
Kvatyuk
M
M
Lu
T
T
Coffman
R L
RL
Pestka
S
S
Rothman
P B
PB
D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D007154:Immune System Diseases / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000235:genetics* / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor