Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor

Gerondakis, S; Strasser, A; Metcalf, D; Grigoriadis, G; Scheerlinck, JPY; Grumont, RJ

Author(s): Gerondakis, S; Strasser, A; Metcalf, D; Grigoriadis, G; Scheerlinck, JPY; Grumont, RJ;
Details: Publication Year 1996-04-16,Volume 93,Issue #8,Page 3405-3409
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
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.
Publisher: NATL ACAD SCIENCES
Keywords: NF-KAPPA-B; C-REL; ACTIVATION; GENE; PROTEINS; PROMOTER; TRANSFORMATION; TRANSCRIPTION; POLYPEPTIDE; DROSOPHILA
Publisher's Version: https://doi.org/10.1073/pnas.93.8.3405
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1996-04-16 12:00:00