title: Overcoming food allergy through acquired tolerance conferred by transfer of Tregs in a murine model.
abstract: BACKGROUND
  The number of food allergy patients is increasing. Some children outgrow their food allergies through tolerance, whereas others remain susceptible throughout their lives. We aimed to contribute to food allergy therapeutics by understanding induction of oral tolerance in a murine food allergy model.
  
  
  METHODS
  We modified an existing murine food allergy model by using ovalbumin (OVA) to induce oral tolerance, either by pretreating mice with OVA or by transferring mesenteric lymph node (MLN) cells or T cells derived from mice treated with OVA.
  
  
  RESULTS
  Pretreatment with OVA prevented food allergy, with complete suppression of OVA-specific immunoglobulin (Ig)E and IgA antibody production and interleukin (IL)-4, IL-10, and IL-9 mRNA expression. The proportion of regulatory T cells (Tregs) in MLN cells and expression of transforming growth factor-β mRNA increased. In the transfer model, anaphylaxis secondary to OVA intake was suppressed by transfer of whole MLN cells and Tregs from OVA-treated mice. However, OVA-specific IgE and IgA expressions were partially attenuated by transfer of antigen-specific and nonspecific Tregs, but not by whole MLN cells from OVA-treated mice. In the Treg transfer model, IL-4 and IL-10 mRNA expression decreased, but IL-9 mRNA expression increased.
  
  
  CONCLUSIONS
  We concluded that oral tolerance for food antigens is induced in two ways: (i) by initial exposure to antigen, or inherent tolerance, and (ii) by transfer of Tregs, or acquired tolerance. Because food allergies occur when inherent tolerance is absent, understanding of acquired tolerance is important for the development of therapies for food allergy.
authors: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Daigakunishi, Japan. hyamashita@gifu-pu.ac.jp
authors: H
authors: H
authors: Yamashita
authors: K
authors: K
authors: Takahashi
authors: H
authors: H
authors: Tanaka
authors: H
authors: H
authors: Nagai
authors: N
authors: N
authors: Inagaki
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer / Q000379:methods*; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D007108:Immune Tolerance / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000485:Allergens; D016207:Cytokines; D007070:Immunoglobulin A; D007073:Immunoglobulin E; D010047:Ovalbumin