1. Interferon regulatory factor-1 is required for a T helper 1 immune response in vivo.
- Author
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Lohoff M, Ferrick D, Mittrucker HW, Duncan GS, Bischof S, Rollinghoff M, and Mak TW
- Subjects
- Animals, CD4-Positive T-Lymphocytes immunology, Cell Differentiation, Cytokines biosynthesis, Immunity, Cellular, Immunity, Innate immunology, Interferon Regulatory Factor-1, Interleukin-12 biosynthesis, Leishmania major, Leishmaniasis, Cutaneous immunology, Lymph Nodes cytology, Lymphocyte Cooperation, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Th1 Cells cytology, Th2 Cells immunology, DNA-Binding Proteins physiology, Phosphoproteins physiology, Th1 Cells immunology
- Abstract
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 IFNgamma 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.
- Published
- 1997
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