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 Leishmania-specific IgG1 and IgE, and their CD4+ T cells produced increased IL-4, characteristics of the non-protective 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.
Lohoff, M., Ferrick, D., Mittrücker, H. W., Duncan, G. on S., Bischof, S., Röllinghoff, M., & Mak, T. W. (1997). Interferon regulatory factor-1 is required for a T helper 1 immune response in vivo. Immunity, 6(6), 681–689. https://doi.org/10.1016/S1074-7613(00)80444-6