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 IFN gamma production. IRF-1(-/-) mice showed dramatically exacerbated Leishmaniasis. They produced increased Leishmania-specific IgG1 and IgE, and their CD4(+) T cells produced increased IL-4, characteristics of the nonprotective Th2 response. In eel 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.