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CD4(+) and CD8(+) T cells play a central role in a HDM driven model of allergic asthma

BACKGROUND: The incidence of asthma is increasing at an alarming rate and while the current available therapies are effective in the majority of patients they fail to adequately control symptoms at the more severe end of the disease spectrum. In the search to understand disease pathogenesis and find...

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Autores principales: Raemdonck, Kristof, Baker, Katie, Dale, Nicole, Dubuis, Eric, Shala, Fisnik, Belvisi, Maria G., Birrell, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845490/
https://www.ncbi.nlm.nih.gov/pubmed/27112462
http://dx.doi.org/10.1186/s12931-016-0359-y
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author Raemdonck, Kristof
Baker, Katie
Dale, Nicole
Dubuis, Eric
Shala, Fisnik
Belvisi, Maria G.
Birrell, Mark A.
author_facet Raemdonck, Kristof
Baker, Katie
Dale, Nicole
Dubuis, Eric
Shala, Fisnik
Belvisi, Maria G.
Birrell, Mark A.
author_sort Raemdonck, Kristof
collection PubMed
description BACKGROUND: The incidence of asthma is increasing at an alarming rate and while the current available therapies are effective in the majority of patients they fail to adequately control symptoms at the more severe end of the disease spectrum. In the search to understand disease pathogenesis and find effective therapies animal models are often employed. As exposure to house dust mite (HDM) has a causative link, it is thought of as the allergen of choice for modelling asthma. The objective was to develop a HDM driven model of asthmatic sensitisation and characterise the role of key allergic effector cells/mediators. METHODS: Mice were sensitised with low doses of HDM and then subsequently challenged. Cellular inflammation, IgE and airway responsiveness (AHR) was assessed in wild type mice or CD4(+)/CD8(+) T cells, B cells or IgE knock out mice. RESULTS: Only those mice sensitised with HDM responded to subsequent low dose topical challenge. Similar to the classical ovalbumin model, there was no requirement for systemic alum sensitisation. Characterisation of the role of effector cells demonstrated that the allergic cellular inflammation and AHR was dependent on CD4(+) and CD8(+) T cells but not B cells or IgE. Finally, we show that this model, unlike the classic OVA model, appears to be resistant to developing tolerance. CONCLUSIONS: This CD4(+)/CD8(+) T cell dependent, HDM driven model of allergic asthma exhibits key features of asthma. Furthermore, we suggest that the ability to repeat challenge with HDM means this model is amenable to studies exploring the effect of therapeutic dosing in chronic, established disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-016-0359-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-48454902016-04-27 CD4(+) and CD8(+) T cells play a central role in a HDM driven model of allergic asthma Raemdonck, Kristof Baker, Katie Dale, Nicole Dubuis, Eric Shala, Fisnik Belvisi, Maria G. Birrell, Mark A. Respir Res Research BACKGROUND: The incidence of asthma is increasing at an alarming rate and while the current available therapies are effective in the majority of patients they fail to adequately control symptoms at the more severe end of the disease spectrum. In the search to understand disease pathogenesis and find effective therapies animal models are often employed. As exposure to house dust mite (HDM) has a causative link, it is thought of as the allergen of choice for modelling asthma. The objective was to develop a HDM driven model of asthmatic sensitisation and characterise the role of key allergic effector cells/mediators. METHODS: Mice were sensitised with low doses of HDM and then subsequently challenged. Cellular inflammation, IgE and airway responsiveness (AHR) was assessed in wild type mice or CD4(+)/CD8(+) T cells, B cells or IgE knock out mice. RESULTS: Only those mice sensitised with HDM responded to subsequent low dose topical challenge. Similar to the classical ovalbumin model, there was no requirement for systemic alum sensitisation. Characterisation of the role of effector cells demonstrated that the allergic cellular inflammation and AHR was dependent on CD4(+) and CD8(+) T cells but not B cells or IgE. Finally, we show that this model, unlike the classic OVA model, appears to be resistant to developing tolerance. CONCLUSIONS: This CD4(+)/CD8(+) T cell dependent, HDM driven model of allergic asthma exhibits key features of asthma. Furthermore, we suggest that the ability to repeat challenge with HDM means this model is amenable to studies exploring the effect of therapeutic dosing in chronic, established disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-016-0359-y) contains supplementary material, which is available to authorized users. BioMed Central 2016-04-25 2016 /pmc/articles/PMC4845490/ /pubmed/27112462 http://dx.doi.org/10.1186/s12931-016-0359-y Text en © Raemdonck et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Raemdonck, Kristof
Baker, Katie
Dale, Nicole
Dubuis, Eric
Shala, Fisnik
Belvisi, Maria G.
Birrell, Mark A.
CD4(+) and CD8(+) T cells play a central role in a HDM driven model of allergic asthma
title CD4(+) and CD8(+) T cells play a central role in a HDM driven model of allergic asthma
title_full CD4(+) and CD8(+) T cells play a central role in a HDM driven model of allergic asthma
title_fullStr CD4(+) and CD8(+) T cells play a central role in a HDM driven model of allergic asthma
title_full_unstemmed CD4(+) and CD8(+) T cells play a central role in a HDM driven model of allergic asthma
title_short CD4(+) and CD8(+) T cells play a central role in a HDM driven model of allergic asthma
title_sort cd4(+) and cd8(+) t cells play a central role in a hdm driven model of allergic asthma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845490/
https://www.ncbi.nlm.nih.gov/pubmed/27112462
http://dx.doi.org/10.1186/s12931-016-0359-y
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