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How T cells regulate interleukin 4 (IL-4) expression is not completely understood. We show here that single-positive thymocytes express IL-4, but attenuate GATA-3 expression, recruit DNA methyltransferases (Dnmts) to the Il4-Il13 locus and downregulate IL-4 expression as they mature into T cells. Type 2 polarization blocks Dnmt1 recruitment, enhances(More)
Interferon-gamma (IFN-gamma) is produced by natural killer cells and certain subsets of T cells, but the basis for its selective expression is unknown. Within the region between -108 and -40 base pairs of the IFN-gamma promoter are two conserved and essential regulatory elements, which confer activation-specific expression in T cells. This report describes(More)
Nuclear factor of activated T cells (NFAT) plays an important role in expression of many cytokine genes including interleukin-2 and interleukin-4. However, its role in interferon-gamma (IFN-gamma) expression is not well understood. In the current studies, two strong NFAT-binding sites in the IFN-gamma promoter were identified by DNase I footprint analysis(More)
The role of DNA methylation and of the maintenance DNA methyltransferase Dnmt1 in the epigenetic regulation of developmental stage- and cell lineage-specific gene expression in vivo is uncertain. This is addressed here through the generation of mice in which Dnmt1 was inactivated by Cre/loxP-mediated deletion at sequential stages of T cell development.(More)
Our understanding of mechanisms by which the expression of IFN-gamma is regulated is limited. Herein, we identify two evolutionarily conserved noncoding sequence elements (IFNgCNS1 and IFNg CNS2) located approximately 5 kb upstream and approximately 18 kb downstream of the initiation codon of the murine Ifng gene. When linked to the murine Ifng gene (-3.4(More)
Group B streptococci (GBS) lack catalase, and they produce and release H2O2;thus, they should be readily killed by phagocytes with a diminished respiratory burst. Surprisingly, although strains of Staphylococcus aureus were killed at H2O2 concentrations greater than 0.5 mM, GBS strains were killed only at concentrations greater than 5mM. In contrast, GBS(More)
To determine whether the production and secretion of TNF and IL-1 by human mononuclear phagocytes could be independently modulated, we examined secretion of TNF and IL-1 by fresh monocytes and monocytes pretreated with IFN-gamma or granulocyte macrophage CSF before LPS stimulation. TNF and IL-1 secretion were in part differentially modulated. Fresh(More)
Like interleukin 2 (IL-2), interferon gamma (IFN-gamma) is an early response gene in T cells and both are prototypical T helper cell type 1 (Th-1) lymphokines. Yet IL-2 and IFN-gamma production are independently regulated, as demonstrated by their differential expression in certain T cell subsets, suggesting that the regulatory elements in these two genes(More)
Lymphotoxin (LT) and tumor necrosis factor (TNF) are related cytokines that share many biological effects. The genes for LT and TNF are adjacent to each other on chromosome 6 in man, but previous data indicate that the kinetics of their production differ markedly. To explain the mechanisms for this difference, we compared the regulation of these two genes(More)
T cell precursors are first detected in the thymus at eight weeks of gestation. By 15 to 20 weeks of gestation, T-cell precursors expressing alpha beta and gamma delta T-cell receptors are present in the thymus in numbers relatively similar to those found in postnatal life. However, recent data suggest that T-cell receptor diversity is more limited during(More)