Original Paper

IL-10-Inducing Adjuvants Enhance Sublingual Immunotherapy Efficacy in a Murine Asthma Model
Laurence Van Overtvelt, Vincent Lombardi, Alain Razafindratsita, Nathalie Saint-Lu, Stéphane Horiot, Hélène Moussu, Laurent Mascarell, Philippe Moingeon

Research and Development, Stallergènes SA, Antony, France

Address of Corresponding Author

Int Arch Allergy Immunol 2008;145:152-162 (DOI: 10.1159/000108140)

  Key Words

• Adjuvants
• Allergy vaccines
• Dendritic cells
• 1,25-Dihydroxyvitamin D3
• Glucocorticoids
• Lactobacillus
• Regulatory T cells
• Sublingual immunotherapy

  Abstract

Background: IL-10-inducing adjuvants could enhance the efficacy of allergy vaccines in establishing allergen-specific tolerance.The aim of this study wasto identify such adjuvants using in vitro cultures of human and murine cells and to evaluate them in a therapeutic murine model of sublingual immunotherapy (SLIT). Methods: Adjuvants stimulating IL-10 gene expression by human or murine immune cells were tested sublingually in BALB/c mice sensitized to ovalbumin (OVA), assessing the reduction in airway hyperresponsiveness (AHR) by whole-body plethysmography. The induction of regulatory T cells (T_reg) was evaluated using phenotypic and functional assays. T-cell proliferation in cervical lymph nodes (LNs) was assessed following intravenous transfer of CFSE-labelled OVA-specific T cells and FACS analysis. Results: A combination of 1,25-dihydroxyvitamin D3 plus dexamethasone (VitD3/Dex) as well as Lactobacillus plantarum were found to induce IL-10 production by human and murine dendritic cells (DCs). The former inhibits LPS-induced DC maturation, whereas L. plantarum induces DC maturation. Following stimulation with VitD3/Dex-pretreated DCs, CD4+ naïve T cells exhibit a T_reg profile.In contrast, a Th1/T_reg pattern of differentiation is observed in the presence of DCs treated with L. plantarum. Both adjuvants significantly enhance SLIT efficacy in mice, in association with either induction of Foxp3+ T_reg cells (for VitD3/Dex) or proliferation of OVA-specific T cells in cervical LNs (for L. plantarum). Conclusions: Both VitD3/Dex and L. plantarum polarize naïve T cells towards IL-10-expressing T cells, through distinct mechanisms. As adjuvants, they both enhance SLIT efficacy in a murine asthma model.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Correspondence to: Dr. Philippe Moingeon
Research and Development, Stallergènes SA
6 rue Alexis de Tocqueville
FR-92160 Antony (France)
Tel. + 33 1 55 59 25 20, Fax + 33 1 55 59 21 02, E-Mail pmoingeon@stallergenes.fr

  Article Information

Received: March 6, 2007
Accepted after revision: May 24, 2007
Published online: September 11, 2007
Number of Print Pages : 11
Number of Figures : 8, Number of Tables : 0, Number of References : 51