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Vol. 145, No. 2, 2008
Issue release date: January 2008
Section title: Original Paper
Int Arch Allergy Immunol 2008;145:152–162
(DOI:10.1159/000108140)

IL-10-Inducing Adjuvants Enhance Sublingual Immunotherapy Efficacy in a Murine Asthma Model

Van Overtvelt L. · Lombardi V. · Razafindratsita A. · Saint-Lu N. · Horiot S. · Moussu H. · Mascarell L. · Moingeon P.
Research and Development, Stallergènes SA, Antony, France

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 3/6/2007
Accepted: 5/24/2007
Published online: 9/11/2007

Number of Print Pages: 11
Number of Figures: 8
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA

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 (Treg) 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 Treg profile.In contrast, a Th1/Treg 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+ Treg 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.


  

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

  

Publication Details

International Archives of Allergy and Immunology

Vol. 145, No. 2, Year 2008 (Cover Date: January 2008)

Journal Editor: Valenta, R. (Vienna)
ISSN: 1018–2438 (print), 1423–0097 (Online)

For additional information: http://www.karger.com/IAA


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 3/6/2007
Accepted: 5/24/2007
Published online: 9/11/2007

Number of Print Pages: 11
Number of Figures: 8
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


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