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

Details

Serval ID
serval:BIB_2AB6616BF8CF
Type
Article: article from journal or magazin.
Collection
Publications
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
J Immunol
Author(s)
Fear V. S., Burchell J. T., Lai S. P., Wikstrom M. E., Blank F., von Garnier C., Turner D. J., Sly P. D., Holt P. G., Strickland D. S., Stumbles P. A.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
2011
Volume
187
Number
9
Pages
4561-70
Language
english
Notes
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
eng
Research Support, Non-U.S. Gov't
J Immunol. 2011 Nov 1;187(9):4561-70. doi: 10.4049/jimmunol.1004189. Epub 2011 Sep 19.
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 CD11b(lo) and CD11b(hi) AMDC and the delivery of OVA to airway draining lymph nodes by CD8alpha(-) 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.
Keywords
Administration, Inhalation, Allergens/*administration & dosage/immunology/toxicity, Amino Acid Sequence, Animals, Bone Marrow Cells/immunology/metabolism, Bronchial Hyperreactivity/immunology/pathology, CD4-Positive T-Lymphocytes/cytology/*immunology/metabolism, *Cell Proliferation, Cells, Cultured, Dendritic Cells/cytology/*immunology/metabolism, Disease Models, Animal, Epitopes, T-Lymphocyte/administration & dosage/*immunology, Female, *Immune Tolerance, Mice, Mice, Inbred BALB C, Mice, Transgenic, Molecular Sequence Data, Ovalbumin/*administration & dosage/immunology/toxicity, Peptide Fragments/*administration & dosage/immunology/toxicity, Respiratory Mucosa/cytology/*immunology/metabolism, Stem Cells/cytology/immunology/metabolism
Pubmed
Create date
15/04/2021 9:58
Last modification date
01/05/2021 5:33
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