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International Immunology Advance Access originally published online on April 18, 2005
International Immunology 2005 17(6):705-712; doi:10.1093/intimm/dxh250
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

Suppression of serum IgE response and systemic anaphylaxis in a food allergy model by orally administered high-dose TGF-ß

Atsushi Okamoto1,2, Tatsuyoshi Kawamura3, Kaori Kanbe1, Yutaka Kanamaru4, Hideoki Ogawa4, Ko Okumura4,5 and Atsuhito Nakao1,4

1 Department of Immunology, 2 Department of Otorhinolaryngology, Head and Neck Surgery and 3 Department of Dermatology, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Tamaho, Yamanashi 409-3898, Japan
4 Atopy Research Center and 5 Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan

Correspondence to: A. Nakao; E-mail: anakao{at}yamanashi.ac.jp

Some epidemiological or association studies suggest that transforming growth factor-ß (TGF-ß) in breast milk may be a decisive factor in diminishing the risk of allergic diseases during infancy. The observations have prompted us to investigate whether TGF-ß, when taken orally, can affect allergic immune responses. Repeated high-dose ovalbumin peptide (OVA) feeding was previously reported to induce OVA-specific IgE production and an anaphylactic reaction after intravenous challenge of OVA in OVA-TCR transgenic mice, which might represent a model for food allergy. By using this model, we showed here that oral administration of high-dose TGF-ß simultaneously with OVA feeding significantly inhibited the OVA-specific IgE elevation and anaphylactic reaction in OVA-TCR transgenic DO11.10 mice. These effects were associated with suppression of OVA-specific IL-4 production and GATA-3 expression and with up-regulation of IFN-{gamma} production and T-bet expression by splenocytes. Intra-peritoneal injection of anti-TGF-ß-neutralizing antibody abolished the inhibitory effects of orally administered TGF-ß on the serum IgE response and anaphylactic reaction after OVA feeding in DO11.10 mice. Interestingly, oral administration of high-dose TGF-ß suppressed activation-induced T cell death induced by OVA feeding in DO11.10 mice. We thus conclude that TGF-ß, when taken orally at high dose, has the capacity to modulate a food allergy-related reaction, at least in part, through its systemic activity.

Keywords: food allergy, IgE, Th2

Transmitting editor: H. Karasuyama


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