title: In vivo inhibition of NF-kappa B in T-lineage cells leads to a dramatic decrease in cell proliferation and cytokine production and to increased cell apoptosis in response to mitogenic stimuli, but not to abnormal thymopoiesis.
abstract: To understand the role of NF-kappa B complexes in T cell development and activation, we have generated transgenic mice in which RelA and c-Rel complexes were selectively inhibited in the T-lineage cells by specific expression of a trans-dominant form of I kappa B alpha. Transgene expression did not affect the thymic development, but led to lowered numbers of splenic T cells and to a dramatic decrease in the ex vivo proliferative response of splenic T lymphocytes. Analysis of IL-2 and IL-2R alpha expression demonstrated that the perturbation of the proliferation response was not attributable to an abnormal expression of these genes. In contrast, expression of IL-4, IL-10, and IFN-gamma was strongly inhibited in the transgenic T cells. The proliferative deficiency of the transgenic T cells was associated with an increased apoptosis. These results point out the involvement of NF-kappa B/Rel family proteins in growth signaling pathways by either regulating proteins involved in the IL-2 signaling or by functionally interfering with the cell cycle progression.
authors.affiliation: Laboratoire d'Immunologie Cellulaire et Tissulaire, Centre National de la Recherche Scientifique UMR 7627, Hôpital de la Pitié-Salpêtrière, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Ferreira
authors.forename: N
authors.initials: N
authors.lastname: Sidénius
authors.forename: N
authors.initials: N
authors.lastname: Tarantino
authors.forename: P
authors.initials: P
authors.lastname: Hubert
authors.forename: L
authors.initials: L
authors.lastname: Chatenoud
authors.forename: F
authors.initials: F
authors.lastname: Blasi
authors.forename: M
authors.initials: M
authors.lastname: Körner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D019076:Transgenes / Q000276:immunology
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007376:Interleukin-2; D008934:Mitogens; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D000072000:NF-KappaB Inhibitor alpha; D015847:Interleukin-4; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate