MICE LACKING IL-12 DEVELOP POLARIZED TH1 CELLS DURING VIRAL-INFECTION

Studies in IL-12-deficient mice established the necessity for IL-12 to generate a Thf cytokine response that is often required for eliminati on of intracellular pathogens, In this study, we demonstrate that mice with a targeted disruption of the IL-12p40 and/or p35 gene effectivel y control Liver damage induced by mouse hepatitis virus (MHV) infectio n, similar to wild-type animals, In contrast, MHV-infected IFN-gamma r eceptor-deficient (IFN-gamma R-/-) mice showed an increased susceptibi lity to coronaviral hepatitis, Surprisingly, MHV-infected mice lacking IL-12 produced a polarized Th1-type cytokine response, as evidenced b y high IFN-gamma and nondetectable IL-4 production by CD4(+) splenocyt es and normal virus-specific serum IgG2a/IgG1 ratios, The virus-induce d type 1 cytokine secretion pattern was not reversed in IL-12-deficien t mice by in vivo neutralization of IFN-gamma nor in IFN-gamma R-/- mi ce receiving IL-12-neutralizing Abs. In IL-12-deficient mice, Th1-type responses were also generated upon immunization with inactivated MHV. In contrast, following immunization with keyhole limpet hemocyanin, m ice lacking IL-12 mounted strongly reduced specific IgG2a and increase d IgE responses, indicative of a type 2-dominated cytokine pattern, Th ese findings demonstrate that following a virus infection, IL-12 is no t essential for the generation of polarized T cell type 1 cytokine exp ression and associated immune responses, which is in marked contrast t o nonviral systems, Our data suggest that viruses may selectively indu ce IFN-gamma production and Th1-type immune reactions even in the abse nce of IL-12.