Lipopolysaccharide stimulation of dendritic cells induces interleukin-10 producing allergen-specific T cells in vitro but fails to prevent allergic airway disease.
Dendritic cells (DCs) play an important role in directing naive T cells towards a Th1/Th2 or regulatory T cells (Treg) cell phenotype. In this context, interleukin (IL)-10 has been shown to exhibit immune regulatory capacities. The aim of this study was to delineate the influence of high-IL-10-producing DCs on DC-T-cell interactions in inhibiting allergen-induced airway inflammation and hyperreactivity in a murine model of allergic airway disease. Bone marrow-derived dendritic cells (BMDCs) were generated from hemopoietic progenitors by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF), and stimulated with ovalbumin (OVA) +/- lipopolysaccharide (LPS). The effects of ovalbumin-pulsed BMDCs on cytokine production by allergen-specific naive T cells were studied in vitro. The development of airway inflammation in Balb/c mice was determined after intranasal administration of BMDCs in vivo. LPS stimulation of BMDCs strongly enhanced IL-10 production. Coculture of LPS-modulated DCs exhibiting increased IL-10 production with allergen-specific naive T cells reduced the production of interferon (IFN)-gamma and IL-5, but enhanced the production of IL-10. After blockade with anti-IL-10 plus anti-IL-10-receptor antibodies, the level of IFN-gamma and IL-5 production by cocultured T cells was restored, underlining the regulatory function of IL-10. Intranasal administration of high-IL-10-producing LPS-stimulated, OVA-primed BMDCs prior to repetitive airway allergen challenges resulted in an even enhanced airway inflammation. These data demonstrate that increased IL-10 production by DCs may be a critical element for T-cell activation and differentiation in the context of allergen-induced immune responses in vitro. However, this DC modulation did not translate into suppression of allergic airway disease in vivo.
Department of Pediatric Pneumology and Immunology, Charité, University Medicine Berlin, Germany. birgit.ahrens@charite.de
Birgit
B
Ahrens
Tobias
T
Freund
Ro-Dug
RD
Rha
Anna-Maria
AM
Dittrich
David
D
Quarcoo
Andreas
A
Hutloff
Eckard
E
Hamelmann
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D015848:Interleukin-5; D008070:Lipopolysaccharides; D016753:Interleukin-10; D007371:Interferon-gamma; D010047:Ovalbumin