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  • Title: Oral tolerance and Treg cells are induced in BALB/c mice after gavage with bovine β-lactoglobulin.
    Author: Adel-Patient K, Wavrin S, Bernard H, Meziti N, Ah-Leung S, Wal JM.
    Journal: Allergy; 2011 Oct; 66(10):1312-21. PubMed ID: 21615416.
    Abstract:
    BACKGROUND: Food allergy is considered as resulting from an impaired development or a breakdown of oral tolerance. We aimed to induce oral tolerance to the major cow's milk allergen bovine β-lactoglobulin (BLG) or corresponding trypsin hydrolysates (BLG-Try) and to investigate the mechanisms involved. METHODS: Wild-type BALB/cJ mice were gavaged on days 1-3 and 8-10 with different doses of native BLG (nBLG) or with nBLG-Try and were then sensitized on day 14 by i.p. administration of BLG in alum. Sensitization was assessed by measurement of BLG-specific antibodies in sera and of cytokines secreted by BLG-reactivated splenocytes. Elicitation of the allergic reaction was assessed by measurement of cytokines and mMCP-1 in sera collected 35 min after an oral challenge. Cellular and biochemical markers of the allergic reaction were also analysed in bronchoalveolar lavage fluids (BAL) collected 24 h after intra-nasal challenge. Analysis of the CD4(+) CD25(+) Foxp3(+) cells in different organs obtained 3 days after gavage and in vivo depletion of CD25(+) cells before oral tolerance induction were then performed. RESULTS: Systemic sensitization and elicitation of the allergic reaction were totally inhibited in mice gavaged with 2 mg of nBLG whereas nBLG-Try was far less efficient. A high percentage of CD4(+) Foxp3(+) cells were observed in BAL from tolerant mice, and a negative correlation between the number of eosinophils and the percentage of Foxp3(+) cells was evidenced. Efficient induction of CD4(+) CD25(+) Foxp3(+) cells after nBLG gavage and impaired oral tolerance induction after in vivo depletion of CD25 cells were then demonstrated. CONCLUSION: For the first time, allergen-induced Treg cells that inhibited both the sensitization and the elicitation of the allergic reaction were evidenced in gavaged wild-type mice.
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