Oral tolerance and Treg cells are induced in BALB/c mice after gavage with bovine β-lactoglobulin


  • Edited by: Angela Haczku

Karine Adel-Patient, Laboratoire INRA d’Immuno-Allergie Alimentaire, iBiTec-S – SPI, Bât. 136 – CEA de Saclay 91191 Gif-sur-Yvette Cedex, France.
Tel.: 33 1 69089225
Fax: 33 1 69085907
E-mail: karine.adel-patient@cea.fr


To cite this article: Adel-Patient K, Wavrin S, Bernard H, Meziti N, Ah-Leung S, Wal J-M. Oral tolerance and Treg cells are induced in BALB/c mice after gavage with bovine β-lactoglobulin. Allergy 2011; 66: 1312–1321.


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.