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Essential role of Notch signaling in effector memory CD8(+) T cell–mediated airway hyperresponsiveness and inflammation

Adoptive transfer of in vivo–primed CD8(+) T cells or in vitro–generated effector memory CD8(+) T (T(EFF)) cells restores airway hyperresponsiveness (AHR) and airway inflammation in CD8-deficient (CD8(−/−)) mice. Examining transcription levels, there was a strong induction of Notch1 in T(EFF) cells...

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Autores principales: Okamoto, Masakazu, Takeda, Katsuyuki, Joetham, Anthony, Ohnishi, Hiroshi, Matsuda, Hiroyuki, Swasey, Christina H., Swanson, Bradley J., Yasutomo, Koji, Dakhama, Azzeddine, Gelfand, Erwin W.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373841/
https://www.ncbi.nlm.nih.gov/pubmed/18426985
http://dx.doi.org/10.1084/jem.20072200
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author Okamoto, Masakazu
Takeda, Katsuyuki
Joetham, Anthony
Ohnishi, Hiroshi
Matsuda, Hiroyuki
Swasey, Christina H.
Swanson, Bradley J.
Yasutomo, Koji
Dakhama, Azzeddine
Gelfand, Erwin W.
author_facet Okamoto, Masakazu
Takeda, Katsuyuki
Joetham, Anthony
Ohnishi, Hiroshi
Matsuda, Hiroyuki
Swasey, Christina H.
Swanson, Bradley J.
Yasutomo, Koji
Dakhama, Azzeddine
Gelfand, Erwin W.
author_sort Okamoto, Masakazu
collection PubMed
description Adoptive transfer of in vivo–primed CD8(+) T cells or in vitro–generated effector memory CD8(+) T (T(EFF)) cells restores airway hyperresponsiveness (AHR) and airway inflammation in CD8-deficient (CD8(−/−)) mice. Examining transcription levels, there was a strong induction of Notch1 in T(EFF) cells compared with central memory CD8(+) T cells. Treatment of T(EFF) cells with a γ-secretase inhibitor (GSI) strongly inhibited Notch signaling in these cells, and after adoptive transfer, GSI-treated T(EFF) cells failed to restore AHR and airway inflammation in sensitized and challenged recipient CD8(−/−) mice, or to enhance these responses in recipient wild-type (WT) mice. These effects of GSI were also associated with increased expression of the Notch ligand Delta1 in T(EFF) cells. Treatment of sensitized and challenged WT mice with Delta1-Fc resulted in decreased AHR and airway inflammation accompanied by higher levels of interferon γ in bronchoalveolar lavage fluid. These results demonstrate a role for Notch in skewing the T cell response from a T helper (Th)2 to a Th1 phenotype as a consequence of the inhibition of Notch receptor activation and the up-regulation of the Notch ligand Delta1. These data are the first to show a functional role for Notch in the challenge phase of CD8(+) T cell–mediated development of AHR and airway inflammation, and identify Delta1 as an important regulator of allergic airway inflammation.
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spelling pubmed-23738412008-11-12 Essential role of Notch signaling in effector memory CD8(+) T cell–mediated airway hyperresponsiveness and inflammation Okamoto, Masakazu Takeda, Katsuyuki Joetham, Anthony Ohnishi, Hiroshi Matsuda, Hiroyuki Swasey, Christina H. Swanson, Bradley J. Yasutomo, Koji Dakhama, Azzeddine Gelfand, Erwin W. J Exp Med Articles Adoptive transfer of in vivo–primed CD8(+) T cells or in vitro–generated effector memory CD8(+) T (T(EFF)) cells restores airway hyperresponsiveness (AHR) and airway inflammation in CD8-deficient (CD8(−/−)) mice. Examining transcription levels, there was a strong induction of Notch1 in T(EFF) cells compared with central memory CD8(+) T cells. Treatment of T(EFF) cells with a γ-secretase inhibitor (GSI) strongly inhibited Notch signaling in these cells, and after adoptive transfer, GSI-treated T(EFF) cells failed to restore AHR and airway inflammation in sensitized and challenged recipient CD8(−/−) mice, or to enhance these responses in recipient wild-type (WT) mice. These effects of GSI were also associated with increased expression of the Notch ligand Delta1 in T(EFF) cells. Treatment of sensitized and challenged WT mice with Delta1-Fc resulted in decreased AHR and airway inflammation accompanied by higher levels of interferon γ in bronchoalveolar lavage fluid. These results demonstrate a role for Notch in skewing the T cell response from a T helper (Th)2 to a Th1 phenotype as a consequence of the inhibition of Notch receptor activation and the up-regulation of the Notch ligand Delta1. These data are the first to show a functional role for Notch in the challenge phase of CD8(+) T cell–mediated development of AHR and airway inflammation, and identify Delta1 as an important regulator of allergic airway inflammation. The Rockefeller University Press 2008-05-12 /pmc/articles/PMC2373841/ /pubmed/18426985 http://dx.doi.org/10.1084/jem.20072200 Text en © 2008 Okamoto et al. 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.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Articles
Okamoto, Masakazu
Takeda, Katsuyuki
Joetham, Anthony
Ohnishi, Hiroshi
Matsuda, Hiroyuki
Swasey, Christina H.
Swanson, Bradley J.
Yasutomo, Koji
Dakhama, Azzeddine
Gelfand, Erwin W.
Essential role of Notch signaling in effector memory CD8(+) T cell–mediated airway hyperresponsiveness and inflammation
title Essential role of Notch signaling in effector memory CD8(+) T cell–mediated airway hyperresponsiveness and inflammation
title_full Essential role of Notch signaling in effector memory CD8(+) T cell–mediated airway hyperresponsiveness and inflammation
title_fullStr Essential role of Notch signaling in effector memory CD8(+) T cell–mediated airway hyperresponsiveness and inflammation
title_full_unstemmed Essential role of Notch signaling in effector memory CD8(+) T cell–mediated airway hyperresponsiveness and inflammation
title_short Essential role of Notch signaling in effector memory CD8(+) T cell–mediated airway hyperresponsiveness and inflammation
title_sort essential role of notch signaling in effector memory cd8(+) t cell–mediated airway hyperresponsiveness and inflammation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373841/
https://www.ncbi.nlm.nih.gov/pubmed/18426985
http://dx.doi.org/10.1084/jem.20072200
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