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

Research output: Contribution to journalArticleResearchpeer-review

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

Cite this

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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-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.",
author = "Gerondakis, {Steven Demetrious} and Andreas Strasser and Donald Metcalf and George Grigoriadis and Scheerlinck, {Jean-Pierre Yves} and Grumont, {Raelene Joy}",
year = "1996",
doi = "10.1073/pnas.93.8.3405",
language = "English",
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pages = "3405 -- 3409",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
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Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor. / Gerondakis, Steven Demetrious; Strasser, Andreas; Metcalf, Donald; Grigoriadis, George; Scheerlinck, Jean-Pierre Yves; Grumont, Raelene Joy.

In: Proceedings of the National Academy of Sciences, Vol. 93, No. 8, 1996, p. 3405 - 3409.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor

AU - Gerondakis, Steven Demetrious

AU - Strasser, Andreas

AU - Metcalf, Donald

AU - Grigoriadis, George

AU - Scheerlinck, Jean-Pierre Yves

AU - Grumont, Raelene Joy

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

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M3 - Article

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JO - Proceedings of the National Academy of Sciences of the United States of America

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