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Restricted aeroallergen access to airway mucosal dendritic cells in vivo limits allergen-specific CD4+ T cell proliferation during the induction of inhalation tolerance.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Nov 01; Vol. 187 (9), pp. 4561-70. Date of Electronic Publication: 2011 Sep 19. - Publication Year :
- 2011
-
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 CD8α(-) 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.
- Subjects :
- Administration, Inhalation
Allergens immunology
Allergens toxicity
Amino Acid Sequence
Animals
Bone Marrow Cells immunology
Bone Marrow Cells metabolism
Bronchial Hyperreactivity immunology
Bronchial Hyperreactivity pathology
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes metabolism
Cells, Cultured
Dendritic Cells cytology
Dendritic Cells metabolism
Disease Models, Animal
Epitopes, T-Lymphocyte administration & dosage
Female
Mice
Mice, Inbred BALB C
Mice, Transgenic
Molecular Sequence Data
Ovalbumin immunology
Ovalbumin toxicity
Peptide Fragments immunology
Peptide Fragments toxicity
Respiratory Mucosa cytology
Respiratory Mucosa metabolism
Stem Cells cytology
Stem Cells immunology
Stem Cells metabolism
Allergens administration & dosage
CD4-Positive T-Lymphocytes immunology
Cell Proliferation
Dendritic Cells immunology
Epitopes, T-Lymphocyte immunology
Immune Tolerance
Ovalbumin administration & dosage
Peptide Fragments administration & dosage
Respiratory Mucosa immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 187
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21930961
- Full Text :
- https://doi.org/10.4049/jimmunol.1004189