Deficiency in the Transcription Factor Interferon Regulatory Factor (Irf)-2 Leads to Severely Compromised Development of Natural Killer and T Helper Type 1 Cells
Copyright policy )Deficiency in the Transcription Factor Interferon Regulatory Factor (Irf)-2 Leads to Severely Compromised Development of Natural Killer and T Helper Type 1 Cells
Interferon (IFN) regulatory factor (IRF)-2 was originally described as an antagonist of IRF-1–mediated transcriptional regulation of IFN-inducible genes. IRF-1−/− mice exhibit defective T helper type 1 (Th1) cell differentiation. We have used experimental leishmaniasis to show that, like IRF-1−/− mice, IRF-2−/− mice are susceptible to Leishmania major infection due to a defect in Th1 differentiation. Natural killer (NK) cell development is compromised in both IRF-1−/− and IRF-2−/− mice, but the underlying mechanism differs. NK (but not NK+ T) cell numbers are decreased in IRF-2−/− mice, and the NK cells that are present are immature in phenotype. Therefore, like IRF-1, IRF-2 is required for normal generation of Th1 responses and for NK cell development in vivo. In this particular circumstance the absence of IRF-2 cannot be compensated for by the presence of IRF-1 alone. Mechanistically, IRF-2 may act as a functional agonist rather than antagonist of IRF-1 for some, but not all, IFN-stimulated regulatory element (ISRE)-responsive genes.
- University of California, Davis United States
- Universitätsklinikum Erlangen Germany
- Institut für Geschichtliche Landeskunde Rheinland-Pfalz e.V. Germany
- University of Toronto Canada
- Institut für Immunologie Germany
CD4-Positive T-Lymphocytes, Interleukin-15, Male, Mice, Knockout, Mice, Inbred BALB C, Leishmaniasis, Cutaneous, Cell Differentiation, Interleukin-12, DNA-Binding Proteins, Killer Cells, Natural, Mice, Inbred C57BL, Disease Models, Animal, Mice, Bone Marrow, Animals, Female, Disease Susceptibility, Lymphocyte Count, Interferon Regulatory Factor-2, Leishmania major
CD4-Positive T-Lymphocytes, Interleukin-15, Male, Mice, Knockout, Mice, Inbred BALB C, Leishmaniasis, Cutaneous, Cell Differentiation, Interleukin-12, DNA-Binding Proteins, Killer Cells, Natural, Mice, Inbred C57BL, Disease Models, Animal, Mice, Bone Marrow, Animals, Female, Disease Susceptibility, Lymphocyte Count, Interferon Regulatory Factor-2, Leishmania major
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