Article: article from journal or magazin.
Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF- plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens.
Journal of Immunology
We generated transgenic mice for STAT-4, a regulatory protein specifically associated with IL-12 signaling, under the control of a CMV promoter. These mice expressed strikingly increased nuclear STAT-4 levels in lamina propria CD4+ T lymphocytes upon systemic administration of dinitrophenyl-keyhole limpet hemocyanin and developed chronic transmural colitis characterized by infiltrates of mainly CD4+ T lymphocytes. The latter cells produced predominantly TNF and IFN-gamma but not IL-4 upon activation with alphaCD3/CD28 or autologous bacterial Ags, consistent with a Th1-type cell response. Furthermore, chronic colitis in STAT-4 transgenic mice could be adoptively transferred to SCID mice by colonic and splenic CD4+ T cells that were activated with Ags from autologous bacterial flora. These data establish a critical molecular signaling pathway involving STAT-4 for the pathogenesis of chronic intestinal inflammation, and targeting of this pathway may be relevant for the treatment of colitis in humans.
Adoptive Transfer/methods, Animals, Antigens, Bacterial/immunology, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/metabolism, Chronic Disease, Colitis/genetics, Colitis/immunology, Crosses, Genetic, Cytokines/biosynthesis, DNA-Binding Proteins/biosynthesis, DNA-Binding Proteins/genetics, Haptens/immunology, Hemocyanin/immunology, Interferon-gamma/biosynthesis, Intestinal Mucosa/metabolism, Intestinal Mucosa/microbiology, Lymphocyte Activation/immunology, Mice, Mice, Inbred Strains, Mice, SCID, Mice, Transgenic, STAT4 Transcription Factor, Signal Transduction/genetics, Signal Transduction/immunology, Trans-Activators/biosynthesis, Trans-Activators/genetics, Tumor Necrosis Factor-alpha/biosynthesis
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