The Cd28/Ctla-4-b7 Signaling Pathway is Involved in Both Allergic Sensitization and Tolerance Induction to Orally Administered Peanut Proteins.
From: Utrecht University, Institute for Risk Assessment Sciences, Department of Immunotoxicology, Utrecht, The Netherlands. F.van.Wijk@umcutrecht.nl
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Jun 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 11
- Pages: 6894-900
- Medium: Print
- Language: English
- Citation (JAMA): van Wijk Femke, Nierkens Stefan, de Jong Wilco, et al. The Cd28/Ctla-4-b7 Signaling Pathway is Involved in Both Allergic Sensitization and Tolerance Induction to Orally Administered Peanut Proteins.. J. Immunol. Jun 2007;178:6894-900
Abstract
Dendritic cells are believed to play an essential role in regulating the balance between immunogenic and tolerogenic responses to mucosal Ags by controlling T cell differentiation and activation via costimulatory and coinhibitory signals. The CD28/CTLA-4-CD80/CD86 signaling pathway appears to be one of the most important regulators of T cell responses but its exact role in responses to orally administered proteins remains to be elucidated. In the present study, the involvement of the CD28/CTLA-4-CD80/CD86 costimulatory pathway in the induction of allergic sensitization and oral tolerance to peanut proteins was investigated. In both an established C3H/HeOuJ mouse model of peanut hypersensitivity and an oral tolerance model to peanut, CD28/CTLA-4-CD80/CD86 interactions were blocked using the fusion protein CTLA-4Ig. To examine the relative contribution of CD80- and CD86-mediated costimulation in these models, anti-CD80 and anti-CD86 blocking Abs were used. In the hypersensitivity model, CTLA-4Ig treatment prevented the development of peanut extract-induced cytokine responses, peanut extract-specific IgG1, IgG2a, and IgE production and peanut extract-induced challenge responses. Blocking of CD80 reduced, whereas anti-CD86 treatment completely inhibited, the induction of peanut extract-specific IgE. Normal tolerance induction to peanut extract was found following CTLA-4Ig, anti-CD86, or anti-CD80 plus anti-CD86 treatment, whereas blockade of CD80 impaired the induction of oral tolerance. We show that CD28/CTLA-4-CD80/CD86 signaling is essential for the development of allergic responses to peanut and that CD86 interaction is most important in inducing peanut extract-specific IgE responses. Additionally, our data suggest that CD80 but not CD86 interaction with CTLA-4 is crucial for the induction of low dose tolerance to peanut.
Mesh Headings (Keywords): Administration, Oral, Allergens, Animals, Antibodies, Blocking, Antigens, CD, Antigens, CD28, Antigens, CD80, Antigens, Differentiation, Arachis hypogaea, Cells, Cultured, Disease Models, Animal, Food Hypersensitivity, Immune Tolerance, Immunoconjugates, Immunoglobulin E, Ligands, Mice, Plant Extracts, Plant Proteins, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 17513738
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