TARGETED DISRUPTION OF THE INTERFERON-GAMMA RECEPTOR-2 GENE RESULTS IN SEVERE IMMUNE DEFECTS IN MICE

To study the role of the interferon- (IFN) gamma R2 chain in IFN-gamma signaling acid immune function, IFN-gamma R2-deficient mice have been generated and characterized. Cells derived from IFN-gamma R2 -/- mice are unable to activate either JAK/STAT signaling proteins or gene tra nscription in response to IFN-gamma. The lack of IFN-gamma responsiven ess 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 t he IFN-gamma R2 -/- mice have a defect in Th1 cell differentiation. Th e IFN-gamma R2 (-/-) mice also produce lower amounts of IFN-gamma in r esponse to antigenic challenge. In addition, IFN-gamma R2 -/- mice are defective in contact hypersensitivity and are highly susceptible to i nfection by Listeria monocytogenes. These results demonstrate that the IFN-gamma R2 is essential for IFN-gamma-mediated immune responses in vivo.