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

Int Immunol. 2005 Jun;17(6):705-12. doi: 10.1093/intimm/dxh250. Epub 2005 Apr 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anaphylaxis / chemically induced
  • Anaphylaxis / immunology
  • Anaphylaxis / prevention & control*
  • Animals
  • Antigens, Differentiation, T-Lymphocyte / drug effects
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Apoptosis / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cytokines / metabolism
  • Fas Ligand Protein
  • Food Hypersensitivity / prevention & control*
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Injections, Subcutaneous
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Spleen / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / metabolism*
  • Transforming Growth Factor beta / administration & dosage
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Necrosis Factors / metabolism


  • Antigens, Differentiation, T-Lymphocyte
  • Cytokines
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Immunoglobulin G
  • Membrane Glycoproteins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factors
  • Immunoglobulin E
  • Ovalbumin