Eradication of a given pathogen is dependent on the selective differentiation of T helper (Th) cells into Th1 or Th2 types. We show here that T cells from mice lacking the transcription factor IRF-1 fail to mount Th1 responses and instead exclusively undergo Th2 differentiation in vitro. Compromised Th1 differentiation is found to be associated with defects in multiple cell types, namely impaired production of interleukin-12 by macrophages, hyporesponsiveness of CD4+ T cells to interleukin-12, and defective development of natural killer cells. These results indicate the involvement of IRF-1 in multiple stages of the Th1 limb of the immune response.

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Magnetic nanoparticles (MNPs) have proven themselves to be useful in biomedical research; however, previous reports were insufficient to address the potential dangers of nanoparticles. Here, we investigated gene expression and metabolic changes based on the microarray and gas chromatographyÀmass spectrometry with human embryo kidney 293 cells treated with MNPs@SiO 2 (RITC), a silicacoated MNP containing Rhodamine B isothiocyanate (RITC). In addition, measurement of reactive oxygen species (ROS) and ATP analysis were performed to evaluate the effect of MNPs@SiO 2 (RITC) on mitochondrial function. Compared to the nontreated control, glutamic acid was increased by more than 2.0-fold, and expression of genes related to the glutamic acid metabolic pathway was also disturbed in 1.0 μg/μL of MNPs@SiO 2 (RITC)-treated cells. Furthermore, increases in ROS concentration and mitochondrial damage were observed in this MNPs@SiO 2 (RITC) concentration. The organic acids related to the Krebs cycle were also disturbed, and the capacity of ATP synthesis was decreased in cell treated with an overdose of MNPs@SiO 2 (RITC). Collectively, these results suggest that overdose (1.0 μg/μL) of MNPs caused transcriptomic and metabolic disturbance. In addition, we suggest that a combination of gene expression and metabolic profiles will provide more detailed and sensitive toxicological evaluation for nanoparticles.