Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma.
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.


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.


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.


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.


CONCLUSIONS
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.
McCarthy
N E
NE
Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, Middlesex, UK.
Jones
H A
HA
Marks
N A
NA
Shiner
R J
RJ
Ind
P W
PW
Al-Hassi
H O
HO
English
N R
NR
Murray
C M
CM
Lambert
J R
JR
Knight
S C
SC
Stagg
A J
AJ
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology; D000704:Analysis of Variance; D018949:Antigens, CD1 / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D015415:Biomarkers; D039521:CD11c Antigen / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D004705:Endocytosis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis; D012137:Respiratory System / Q000276:immunology*; D012882:Skin Tests; D013183:Sputum / Q000276:immunology; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D000485:Allergens; D018949:Antigens, CD1; D015415:Biomarkers; D039521:CD11c Antigen; D019013:CD40 Antigens; D020796:Receptor, Platelet-Derived Growth Factor alpha