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

Steven Demetrious Gerondakis, Andreas Strasser, Donald Metcalf, George Grigoriadis, Jean-Pierre Yves Scheerlinck, Raelene Joy Grumont

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Abstract

The c-rel protooncogene encodes a subunit of the NF-I?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 I? (IL-2RI?) 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 I? (TNF- I?), and I? interferon (IFN-I?) 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- I?, and IFN-I?, 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.
Original languageEnglish
Pages (from-to)3405 - 3409
Number of pages5
JournalProceedings of the National Academy of Sciences
Volume93
Issue number8
DOIs
Publication statusPublished - 1996

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