INTERFERON REGULATORY FACTOR-I IS REQUIRED FOR A T-HELPER-1 IMMUNE-RESPONSE IN-VIVO

The transcription factor interferon regulatory factor-1 (IRF-1) mediat es 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 fro m Leishmania-infected mice lacking one (+/-) or both (-/-) alleles of the IRF-1 gene developed a profound, gene dose-dependent decrease in I FN gamma production. IRF-1(-/-) mice showed dramatically exacerbated L eishmaniasis. 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 o f IRF-1(-/-) mice to produce IL-12 was severely compromised. Thus, IRF -1 is a determining factor for Th1 responses.