CTLA-4 signaling regulates the intensity of hypersensitivity responses to food antigens, but is not decisive in the induction of sensitization.

Abstract

Although food allergy has emerged as a major health problem, the mechanisms that are decisive in the development of sensitization to dietary Ag remain largely unknown. CTLA-4 signaling negatively regulates immune activation, and may play a crucial role in preventing induction and/or progression of sensitization to food Ag. To elucidate the role of CTLA-4 signaling in responses to food allergens, a murine model of peanut allergy was used. During oral exposure to peanut protein extract (PPE) together with the mucosal adjuvant cholera toxin (CT), which induces peanut allergy, CTLA-4 ligation was prevented using a CTLA-4 mAb. Additionally, the effect of inhibition of the CTLA-4 pathway on oral exposure to PPE in the absence of CT, which leads to unresponsiveness to peanut Ag, was explored. During sensitization, anti-CTLA-4 treatment considerably enhanced IgE responses to PPE and the peanut allergens, Ara h 1, Ara h 3, and Ara h 6, resulting in elevated mast cell degranulation upon an oral challenge. Remarkably, antagonizing CTLA-4 during exposure to PPE in the absence of CT resulted in significant induction of Th2 cytokines and an elevation in total serum IgE levels, but failed to induce allergen-specific IgE responses and mast cell degranulation upon a PPE challenge. These results indicate that CTLA-4 signaling is not the crucial factor in preventing sensitization to food allergens, but plays a pivotal role in regulating the intensity of a food allergic sensitization response. Furthermore, these data indicate that a profoundly Th2-biased cytokine environment is insufficient to induce allergic responses against dietary Ag.

• Authors: Femke van Wijk, Sanne Hoeks, Stefan Nierkens, Stef J Koppelman, Peter van Kooten, Louis Boon, Léon M J Knippels, Raymond Pieters
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 1 Pg. 174-9 (Jan 01 2005) ISSN: 0022-1767 [Print] United States
• PMID: 15611239 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Allergens
• Antigens, CD
• Antigens, Differentiation
• CTLA-4 Antigen
• Ctla4 protein, mouse
• Cytokines
• Immunoglobulin E

Topics

• Adjuvants, Immunologic (pharmacology)
• Allergens (immunology)
• Animals
• Antigens, CD
• Antigens, Differentiation (immunology, metabolism)
• CTLA-4 Antigen
• Cytokines (immunology)
• Disease Models, Animal
• Female
• Immunoglobulin E (blood)
• Mast Cells (immunology, metabolism)
• Mice
• Peanut Hypersensitivity (immunology)
• Signal Transduction (immunology)
• Th2 Cells (immunology)