title: Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor.
abstract: The c-rel protooncogene encodes a subunit of the NF-kappa B-like family of transcription factors. Mice lacking Rel are defective in mitogenic activation of B and T lymphocytes and display impaired humoral immunity. In an attempt to identify changes in gene expression that accompany the T-cell stimulation defects associated with the loss of Rel, we have examined the expression of cell surface activation markers and cytokine production in mitogen-stimulated Rel-/- T cells. The expression of cell surface markers including the interleukin 2 receptor alpha (IL-2R alpha) chain (CD25), CD69 and L-selectin (CD62) is normal in mitogen-activated Rel-/- T cells, but cytokine production is impaired. In Rel-/- splenic T cell cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin, the levels of IL-3, IL-5, granulocyte- macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) were only 2- to 3-fold lower compared with normal T cells. In contrast, anti-CD3 and anti-CD28 stimulated Rel-/- T cells, which fail to proliferate, make little or no detectable cytokines. Exogenous IL-2, which restitutes the proliferative response of the anti-CD3- and anti-CD28-treated Rel-/- T cells, restores production of IL-5, TNF-alpha, and IFN-gamma, but not IL-3 and GM-CSF expression to approximately normal levels. In contrast to mitogen-activated Rel-/- T cells, lipopolysaccharide-stimulated Rel-/- macrophages produce higher than normal levels of GM-CSF. These findings establish that Rel can function as an activator or repressor of gene expression and is required by T lymphocytes for production of IL-3 and GM-CSF.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Gerondakis
authors.forename: A
authors.initials: A
authors.lastname: Strasser
authors.forename: D
authors.initials: D
authors.lastname: Metcalf
authors.forename: G
authors.initials: G
authors.lastname: Grigoriadis
authors.forename: J Y
authors.initials: JY
authors.lastname: Scheerlinck
authors.forename: R J
authors.initials: RJ
authors.lastname: Grumont
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007377:Interleukin-3 / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D020569:Proto-Oncogene Proteins c-rel; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D007377:Interleukin-3; D008934:Mitogens; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA