Interferon Regulatory Factor-1 Is Required for a T Helper 1 Immune Response In Vivo

The transcription factor interferon regulatory factor-1 (IRF-1) mediates the effects of IFN. No information exists on its role in lymphokine production. Protection against the intracellular pathogen Leishmania major depends on a Th1 response. Here, we show that CD4 + T cells from Leishmania-infected mice lacking one (+/−) or both (−/−) alleles of the IRF-1 gene developed a profound, gene dose-dependent decrease in IFNγ production. IRF-1 −/− mice showed dramatically exacerbated Leishmaniasis. They produced increased Leish- mania-specific IgG1 and IgE, and their CD4 + T cells produced increased IL-4, characteristics of the nonprotective Th2 response. In cell transfer experiments, IRF-1 −/− CD4 + T cells mounted normal Th1 responses. However, the ability of IRF-1 −/− mice to produce IL-12 was severely compromised. Thus, IRF-1 is a determining factor for Th1 responses.