Restricted aeroallergen access to airway mucosal dendritic cells in vivo limits allergen-specific CD4+T cell proliferation during the induction of inhalation tolerance

Fear, Vanessa S., Burchell, Jennifer T., Lai, Siew Ping, Wikstrom, Matthew E., Blank, Fabian, von Garnier, Christophe, Turner, Debra J., Sly, Peter D., Holt, Patrick G., Strickland, Deborah S. and Stumbles, Philip A. (2011) Restricted aeroallergen access to airway mucosal dendritic cells in vivo limits allergen-specific CD4+T cell proliferation during the induction of inhalation tolerance. Journal of Immunology, 187 9: 4561-4570. doi:10.4049/jimmunol.1004189

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Author Fear, Vanessa S.
Burchell, Jennifer T.
Lai, Siew Ping
Wikstrom, Matthew E.
Blank, Fabian
von Garnier, Christophe
Turner, Debra J.
Sly, Peter D.
Holt, Patrick G.
Strickland, Deborah S.
Stumbles, Philip A.
Title Restricted aeroallergen access to airway mucosal dendritic cells in vivo limits allergen-specific CD4+T cell proliferation during the induction of inhalation tolerance
Formatted title
Restricted aeroallergen access to airway mucosal dendritic cells in vivo limits allergen-specific CD4+T cell proliferation during the induction of inhalation tolerance
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2011-09-19
Sub-type Article (original research)
DOI 10.4049/jimmunol.1004189
Volume 187
Issue 9
Start page 4561
End page 4570
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Collection year 2012
Language eng
Formatted abstract
Chronic innocuous aeroallergen exposure attenuates CD4+ T cell-mediated airways hyperresponsiveness in mice; however, the mechanism(s) remain unclear. We examined the role of airway mucosal dendritic cell (AMDC) subsets in this process using a multi-OVA aerosol-induced tolerance model in sensitized BALB/c mice. Aeroallergen capture by both CD11blo and CD11bhi AMDC and the delivery of OVA to airway draining lymph nodes by CD8a- migratory dendritic cells (DC) were decreased in vivo (but not in vitro) when compared with sensitized but nontolerant mice. This was functionally significant, because in vivo proliferation of OVA-specific CD4+ T cells was suppressed in airway draining lymph nodes of tolerized mice and could be restored by
intranasal transfer of OVA-pulsed and activated exogenous DC, indicating a deficiency in Ag presentation by endogenous DC arriving from the airway mucosa. Bone marrow-derived DC Ag-presenting function was suppressed in multi-OVA tolerized mice, and allergen availability to airway APC populations was limited after multi-OVA exposure, as indicated by reduced OVA and dextran uptake by airway interstitial macrophages, with diffusion rather than localization of OVA across the airway mucosal surface. These data indicate that inhalation tolerance limits aeroallergen capture by AMDC subsets through a mechanism of bone marrow suppression of DC precursor function coupled with reduced Ag availability in vivo at the airway mucosa, resulting in limited Ag delivery to lymph nodes and hypoproliferation of allergen-specific CD4+ T cells.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Health and Behavioural Sciences -- Publications
Official 2012 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
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Created: Fri, 21 Oct 2011, 15:14:30 EST by Roxanne Jemison on behalf of Child Health Research Centre