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Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma.
- Source :
-
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2007 Jan; Vol. 37 (1), pp. 72-82. - Publication Year :
- 2007
-
Abstract
- Background: Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory-tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis.<br />Objective: To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation.<br />Methods: Sputum cells were induced from steroid-naïve, allergen-challenged and allergen-naïve subjects (atopic asthmatics, atopic non-asthmatics and non-atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry.<br />Results: hRTDC stained HLA-DR(+) (negative for markers of other cell lineages) were predominantly myeloid and comprised approximately 0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4(+) naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC-dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05-P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c(-)CD123(high) hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge.<br />Conclusion: Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.
- Subjects :
- Administration, Inhalation
Adult
Aged
Analysis of Variance
Biomarkers
CD11c Antigen analysis
CD40 Antigens analysis
Case-Control Studies
Dendritic Cells immunology
Dendritic Cells physiology
Endocytosis
Female
Flow Cytometry
Humans
Lymphocyte Activation
Male
Microscopy, Immunoelectron
Middle Aged
Receptor, Platelet-Derived Growth Factor alpha analysis
Skin Tests
Sputum immunology
Statistics, Nonparametric
Allergens immunology
Antigens, CD1 immunology
Asthma immunology
Respiratory System immunology
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 0954-7894
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 17210044
- Full Text :
- https://doi.org/10.1111/j.1365-2222.2006.02631.x