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Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling

The cytokines interleukin (IL)-2, IL-4, IL-6, IL-7, and IL-15 have all previously been shown to inhibit resting T cell death in vitro. We have found a difference in the response of T cells to IL-6, depending on the activation status of the cells. IL-6 inhibited the death of naive T cells, but had no...

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Autores principales: Teague, T. Kent, Schaefer, Brian C., Hildeman, David, Bender, Jeremy, Mitchell, Tom, Kappler, John W., Marrack, Philippa
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193120/
https://www.ncbi.nlm.nih.gov/pubmed/10727454
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author Teague, T. Kent
Schaefer, Brian C.
Hildeman, David
Bender, Jeremy
Mitchell, Tom
Kappler, John W.
Marrack, Philippa
author_facet Teague, T. Kent
Schaefer, Brian C.
Hildeman, David
Bender, Jeremy
Mitchell, Tom
Kappler, John W.
Marrack, Philippa
author_sort Teague, T. Kent
collection PubMed
description The cytokines interleukin (IL)-2, IL-4, IL-6, IL-7, and IL-15 have all previously been shown to inhibit resting T cell death in vitro. We have found a difference in the response of T cells to IL-6, depending on the activation status of the cells. IL-6 inhibited the death of naive T cells, but had no effect on the death of either superantigen-activated T cells, or T cells bearing memory markers. This was true even when the resting and activated T cells were isolated from the same animal; thus, the determining factor for IL-6 insensitivity was the activation status or activation history of the cell, and not the milieu in the animal from which the cells were isolated. Activated T cells expressed lower levels of IL-6 receptors on their surfaces, yet there were sufficient levels of receptors for signaling, as we observed similar levels of signal transducer and activator of transcription (Stat)3 phosphorylation in resting and activated T cells treated with IL-6. However, there was profound inhibition of IL-6–induced Stat1 phosphorylation in activated T cells compared with resting T cells. These data suggest that there is activation-induced inhibition of IL-6 receptor signaling in T cells. This inhibition appears to be specific for some but not all of the IL-6–mediated signaling cascades in these cells.
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spelling pubmed-21931202008-04-16 Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling Teague, T. Kent Schaefer, Brian C. Hildeman, David Bender, Jeremy Mitchell, Tom Kappler, John W. Marrack, Philippa J Exp Med Original Article The cytokines interleukin (IL)-2, IL-4, IL-6, IL-7, and IL-15 have all previously been shown to inhibit resting T cell death in vitro. We have found a difference in the response of T cells to IL-6, depending on the activation status of the cells. IL-6 inhibited the death of naive T cells, but had no effect on the death of either superantigen-activated T cells, or T cells bearing memory markers. This was true even when the resting and activated T cells were isolated from the same animal; thus, the determining factor for IL-6 insensitivity was the activation status or activation history of the cell, and not the milieu in the animal from which the cells were isolated. Activated T cells expressed lower levels of IL-6 receptors on their surfaces, yet there were sufficient levels of receptors for signaling, as we observed similar levels of signal transducer and activator of transcription (Stat)3 phosphorylation in resting and activated T cells treated with IL-6. However, there was profound inhibition of IL-6–induced Stat1 phosphorylation in activated T cells compared with resting T cells. These data suggest that there is activation-induced inhibition of IL-6 receptor signaling in T cells. This inhibition appears to be specific for some but not all of the IL-6–mediated signaling cascades in these cells. The Rockefeller University Press 2000-03-20 /pmc/articles/PMC2193120/ /pubmed/10727454 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Teague, T. Kent
Schaefer, Brian C.
Hildeman, David
Bender, Jeremy
Mitchell, Tom
Kappler, John W.
Marrack, Philippa
Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling
title Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling
title_full Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling
title_fullStr Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling
title_full_unstemmed Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling
title_short Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling
title_sort activation-induced inhibition of interleukin 6–mediated t cell survival and signal transducer and activator of transcription 1 signaling
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193120/
https://www.ncbi.nlm.nih.gov/pubmed/10727454
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