IFN-GAMMA RECEPTOR-DEFICIENT MICE GENERATE ANTIVIRAL TH1-CHARACTERISTIC CYTOKINE PROFILES BUT ALTERED ANTIBODY-RESPONSES

The lymphokine IFN-gamma is a pleiotropic immunomodulator and possesse s intrinsic antiviral activity. We studied its significance in the dev elopment of antiviral immune responses by using IFN-gamma receptor-def icient (IFN-gamma R(-/-)) mice. After inoculation with live attenuated pseudorabies virus (PRV), the mutant mice showed no infectivity titer s in various tissues, and transient viral Ag expression only in the sp leen, similar as in wild-type mice. However, the absence of the IFN-ga mma R resulted in increased proliferative splenocyte responses. The PR V-immune animals showed a normal IFN-gamma and IL-2 production, withou t detectable IL-4, and with decreased IL-10 secretion in response to v iral Ag or Con A. Immunohistochemically, an increased ratio of IFN-gam ma:IL-4-producing spleen cells was found. After immunization with eith er live attenuated or inactivated PRV, IFN-gamma R(-/-) mice produced significantly less antiviral Ab, and more succumbed to challenge infec tion than the intact control animals. The reduction in Ab titers in th e mutant mice correlated with lower protection by their sera in transf er experiments. Our data demonstrate that ablation of the IFN-gamma re ceptor surprisingly does not inhibit the generation of antiviral Th1-t ype and increase Th2-type cytokine responses. However, it profoundly i mpairs the generation of protective antiviral Ab.