title: Suppression of serum IgE response and systemic anaphylaxis in a food allergy model by orally administered high-dose TGF-beta.
abstract: Some epidemiological or association studies suggest that transforming growth factor-beta (TGF-beta) 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-beta, 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-beta 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-beta-neutralizing antibody abolished the inhibitory effects of orally administered TGF-beta on the serum IgE response and anaphylactic reaction after OVA feeding in DO11.10 mice. Interestingly, oral administration of high-dose TGF-beta suppressed activation-induced T cell death induced by OVA feeding in DO11.10 mice. We thus conclude that TGF-beta, when taken orally at high dose, has the capacity to modulate a food allergy-related reaction, at least in part, through its systemic activity.
authors.affiliation: Department of Immunology, University of Yamanashi, Tamaho, Yamanashi 409-3898, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okamoto
authors.forename: Tatsuyoshi
authors.initials: T
authors.lastname: Kawamura
authors.forename: Kaori
authors.initials: K
authors.lastname: Kanbe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kanamaru
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000284:Administration, Oral; D000707:Anaphylaxis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D053222:Fas Ligand Protein; D005512:Food Hypersensitivity / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D048069:Tumor Necrosis Factors; D007073:Immunoglobulin E; D010047:Ovalbumin