Allergic airways disease develops after an increase in allergen capture and processing in the airway mucosa.
Airway mucosal dendritic cells (AMDC) and other airway APCs continuously sample inhaled Ags and regulate the nature of any resulting T cell-mediated immune response. Although immunity develops to harmful pathogens, tolerance arises to nonpathogenic Ags in healthy individuals. This homeostasis is thought to be disrupted in allergic respiratory disorders such as allergic asthma, such that a potentially damaging Th2-biased, CD4(+) T cell-mediated inflammatory response develops against intrinsically nonpathogenic allergens. Using a mouse model of experimental allergic airways disease (EAAD), we have investigated the functional changes occurring in AMDC and other airway APC populations during disease onset. Onset of EAAD was characterized by early and transient activation of airway CD4(+) T cells coinciding with up-regulation of CD40 expression exclusively on CD11b(-) AMDC. Concurrent enhanced allergen uptake and processing occurred within all airway APC populations, including B cells, macrophages, and both CD11b(+) and CD11b(-) AMDC subsets. Immune serum transfer into naive animals recapitulated the enhanced allergen uptake observed in airway APC populations and mediated activation of naive allergen-specific, airway CD4(+) T cells following inhaled allergen challenge. These data suggest that the onset of EAAD is initiated by enhanced allergen capture and processing by a number of airway APC populations and that allergen-specific Igs play a role in the conversion of normally quiescent AMDC subsets into those capable of inducing airway CD4(+) T cell activation.
von Garnier
Christophe
C
Telethon Institute for Child Health Research and Centre for Child Health Research, School of Pediatrics and Child Health, University of Western Australia, West Perth, Western Australia, Australia. christophe.vongarnier@insel.ch
Wikstrom
Matthew E
ME
Zosky
Graeme
G
Turner
Debra J
DJ
Sly
Peter D
PD
Smith
Miranda
M
Thomas
Jennifer A
JA
Judd
Samantha R
SR
Strickland
Deborah H
DH
Holt
Patrick G
PG
Stumbles
Philip A
PA
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015415:Biomarkers; D001982:Bronchial Diseases / Q000276:immunology* / Q000503:physiopathology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology* / Q000503:physiopathology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D020545:Respiratory Mucosa / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D000941:Antigens; D015415:Biomarkers