Plasmacytoid dendritic cells activate allergen-specific TH2 memory cells: modulation by CpG oligodeoxynucleotides.
BACKGROUND
Plasmacytoid dendritic cells (PDCs) accumulate in the nasal mucosa of allergic rhinitis patients, but their function in upper airway allergy has not been determined. CpG oligodeoxynucleotides, potent adjuvants in immunotherapeutic strategies in animal models, are especially effective at activating PDCs. These cells are therefore potential targets for immunomodulation in humans.


OBJECTIVE
In this study, PDCs were compared with CD11c+ dendritic cells (DCs), a very potent antigen-presenting cell type, for their capacity to induce allergen-dependent activation of TH2 memory cells. Then, we investigated whether CpG-activated PDCs were able to modulate the allergen-specific TH2 memory response.


METHODS
DCs were isolated from patients with upper airway allergy and cocultured with autologous CD4+ T cells with or without grass pollen extract and CpG. In some experiments cells were restimulated with allergen-pulsed monocyte-derived DCs. T-cell activation was measured by their proliferative response and cytokine production.


RESULTS
PDCs stimulated allergen-dependent T-cell proliferation and TH2 cytokine production as efficiently as CD11c+ DCs. CpG-activated PDCs inhibited allergen-dependent proliferation of TH2 memory cells and markedly increased IFN-gamma production in PDC/T-cell cocultures; the former effect depended on the CpG-induced IFN-alpha/beta production by the PDCs.


CONCLUSIONS
Our results demonstrated that PDCs efficiently drive allergen-dependent TH2 memory responses, suggesting that they play an active role in the allergic reaction. However, in the presence of CpG, PDCs were responsible for increased production of the TH1-related cytokines IFN-alpha and IFN-gamma, indicating that mucosal PDCs may be targets for CpG-based immunotherapeutic strategies against airway allergy.
Section for Immune Regulation and Allergy, LIIPAT, Institute of Pathology, Rikshospitalet University Hospital, Norway. lorant.farkas@labmed.uio.no
Lorant
L
Farkas
Espen O
EO
Kvale
Finn-Eirik
FE
Johansen
Frode L
FL
Jahnsen
Fridtjof
F
Lund-Johansen
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000485:Allergens / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000502:physiology; D016899:Interferon-beta / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D006109:Poaceae / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000485:Allergens; C408982:CPG-oligonucleotide; D016207:Cytokines; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D016899:Interferon-beta; D007371:Interferon-gamma