Multiple T cell epitope peptides suppress allergic responses in an egg allergy mouse model by the elicitation of forkhead box transcription factor 3- and transforming growth factor-beta-associated mechanisms.
BACKGROUND
Peptide-based immunotherapy (PIT) represents an attractive approach for targeted interventions in immunological disorders, but has not been widely explored in the context of food allergy.


OBJECTIVE
In this study, we built on the information obtained from the recent identification of three immunodominant T cell epitopes of hen ovalbumin (OVA), a major egg allergen, to assess the therapeutic potential of PIT for food allergy, using the BALB/c mouse model.


METHODS
Groups of mice were sensitized to OVA by repeated oral gavages, and subsequently administered with single or multiple synthetic peptides containing OVA T cell epitopes. Following the peptide administration period, all mice were orally challenged with high doses of OVA to elicit active anaphylaxis. Serum, spleen, and intestinal tissues were collected for the determination of immunoglobulin levels, cytokine secretions, and intestinal gene expression.


RESULTS
Significantly lower anaphylactic scores were exhibited by mice that received multiple epitope-containing peptides, accompanied by lower serum histamine and OVA-specific IgE levels, compared with placebo-treated mice. Mechanistically, the quantification of cytokine secretions in splenocyte cultures revealed a T helper type 1-biased response (IFN-gamma) in all peptide-treated mice to the detriment of a T helper type 2-response (IL-4). Interestingly, a similar cytokine expression profile was determined in intestinal tissues, accompanied by a pronounced mRNA expression of regulatory molecules TGF-beta and forkhead box transcription factor 3 (FOXP3). These data suggest the activation of local repressive mechanisms mediated by subsets of regulatory T cells.


CONCLUSIONS
We demonstrated the therapeutic potential of PIT in a mouse model of food allergy model and provided evidence that mechanistic pathways entailing regulatory molecules TGF-beta and FOXP3, stand as promising trails for the further understanding of peptide-based strategies for food allergy.
Yang
M
M
Department of Food Science, University of Guelph, ON, Canada.
Yang
C
C
Mine
Y
Y
D000595:Amino Acid Sequence; D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D016207:Cytokines; D004195:Disease Models, Animal; D021181:Egg Hypersensitivity / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D010455:Peptides; D016212:Transforming Growth Factor beta; D010047:Ovalbumin