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CD4(+)CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function

The role of natural CD4(+)CD25(+) regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hy...

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Autores principales: Lewkowich, Ian P., Herman, Nancy S., Schleifer, Kathleen W., Dance, Matthew P., Chen, Brian L., Dienger, Krista M., Sproles, Alyssa A., Shah, Jaimin S., Köhl, Jörg, Belkaid, Yasmine, Wills-Karp, Marsha
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213331/
https://www.ncbi.nlm.nih.gov/pubmed/16314437
http://dx.doi.org/10.1084/jem.20051506
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author Lewkowich, Ian P.
Herman, Nancy S.
Schleifer, Kathleen W.
Dance, Matthew P.
Chen, Brian L.
Dienger, Krista M.
Sproles, Alyssa A.
Shah, Jaimin S.
Köhl, Jörg
Belkaid, Yasmine
Wills-Karp, Marsha
author_facet Lewkowich, Ian P.
Herman, Nancy S.
Schleifer, Kathleen W.
Dance, Matthew P.
Chen, Brian L.
Dienger, Krista M.
Sproles, Alyssa A.
Shah, Jaimin S.
Köhl, Jörg
Belkaid, Yasmine
Wills-Karp, Marsha
author_sort Lewkowich, Ian P.
collection PubMed
description The role of natural CD4(+)CD25(+) regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25–mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell–depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell–depleted C3H mice. T reg cell–depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell–depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4(+)CD25(+) T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.
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spelling pubmed-22133312008-03-11 CD4(+)CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function Lewkowich, Ian P. Herman, Nancy S. Schleifer, Kathleen W. Dance, Matthew P. Chen, Brian L. Dienger, Krista M. Sproles, Alyssa A. Shah, Jaimin S. Köhl, Jörg Belkaid, Yasmine Wills-Karp, Marsha J Exp Med Article The role of natural CD4(+)CD25(+) regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25–mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell–depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell–depleted C3H mice. T reg cell–depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell–depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4(+)CD25(+) T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility. The Rockefeller University Press 2005-12-05 /pmc/articles/PMC2213331/ /pubmed/16314437 http://dx.doi.org/10.1084/jem.20051506 Text en Copyright © 2005, 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 Article
Lewkowich, Ian P.
Herman, Nancy S.
Schleifer, Kathleen W.
Dance, Matthew P.
Chen, Brian L.
Dienger, Krista M.
Sproles, Alyssa A.
Shah, Jaimin S.
Köhl, Jörg
Belkaid, Yasmine
Wills-Karp, Marsha
CD4(+)CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function
title CD4(+)CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function
title_full CD4(+)CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function
title_fullStr CD4(+)CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function
title_full_unstemmed CD4(+)CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function
title_short CD4(+)CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function
title_sort cd4(+)cd25(+) t cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213331/
https://www.ncbi.nlm.nih.gov/pubmed/16314437
http://dx.doi.org/10.1084/jem.20051506
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