International Immunology Advance Access published online on April 18, 2005
International Immunology, doi:10.1093/intimm/dxh250
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1 Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Tamaho, Yamanashi 409-3898, Japan; Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Tamaho, Yamanashi 409-3898, Japan
* To whom correspondence should be addressed. Some epidemiological or association studies suggest that transforming growth factor-
Received December 5, 2004
Accepted March 4, 2005
Article
Suppression of serum IgE response and systemic anaphylaxis in a food allergy model by orally administered high-dose TGF-
2 Department of Dermatology, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Tamaho, Yamanashi 409-3898, Japan
3 Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Tamaho, Yamanashi 409-3898, Japan
4 Atopy Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan
5 Atopy Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan; Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
6 Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Tamaho, Yamanashi 409-3898, Japan; Atopy Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Atsuhito Nakao, E-mail: anakao{at}yamanashi.ac.jp
Abstract 
(TGF-) 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-, 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- 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-
production and T-bet expression by splenocytes. Intra-peritoneal injection of anti-TGF--neutralizing antibody abolished the inhibitory effects of orally administered TGF- on the serum IgE response and anaphylactic reaction after OVA feeding in DO11.10 mice. Interestingly, oral administration of high-dose TGF- suppressed activation-induced T cell death induced by OVA feeding in DO11.10 mice. We thus conclude that TGF-, when taken orally at high dose, has the capacity to modulate a food allergy-related reaction, at least in part, through its systemic activity.
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