title: In Vitro Induction of Allergen-Specific Interleukin-10-Producing Regulatory B Cell Responses by Interferon-γ in Non-Immunoglobulin E-Mediated Milk Allergy.
abstract: OBJECTIVE
  Specific oral immunotherapy (SOIT) using interferon-γ (IFN-γ) has been successful as a food allergy treatment. Interleukin-10 (IL-10)-producing regulatory B cells (Br1s) play a role in immune tolerance to food allergens. In addition, IFN-γ shows tolerogenic effects on allergen-induced Br1 responses.
  
  
  METHODS
  Eleven patients that were allergic to cow's milk and 12 milk-tolerant subjects were selected by double-blind placebo-controlled food challenge (DBPCFC) and clinical characteristics. The immunomodulatory effects of IFN-γ on allergen-specific Br1 responses were evaluated in 6 milk allergy patients and 8 milk-tolerant subjects. Peripheral blood mononuclear cells (PBMCs) from subjects were stimulated with casein and/or IFN-γ and analyzed by flow cytometry.
  
  
  RESULTS
  IFN-γ had no effect on total cell counts or the proportion of Br1 cells in PBMCs. IFN-γ stimulation did not change total Br1 cell counts or the percentage of Br1s among CD5(+) B cells in the milk allergy or the milk-tolerant groups. In the milk allergy group, Br1 counts were not different between the control and the casein stimulation but significantly increased in the IFN-γ + casein stimulated cells, and the Br1 fractions were decreased after casein stimulation and recovered in the addition of IFN-γ for stimulation. In the milk-tolerant group, Br1 counts increased in the casein stimulated cells and in the IFN-γ + casein stimulated cells, but the increase was significantly less when IFN-γ was added, and the Br1 fractions were increased after casein stimulation and IFN-γ + casein stimulation, that was not significant when IFN-γ was added.
  
  
  CONCLUSIONS
  IFN-γ-induced allergen-specific Br1 responses in the PBMCs of milk allergy patients play a role in milk allergen-specific tolerance induction in vitro. Further investigations into the molecular immunological mechanisms underlying the induction of allergen-specific Br1 responses are needed.
authors.affiliation: Department of Pediatrics, College of Medicine, Eulji University, Daejeon, Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Geunwoong
authors.initials: G
authors.lastname: Noh
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
keywords: Atopic dermatitis; IFN-γ; IL-10-producing regulatory B cell; non-IgE-mediated milk allergy; oral immunotherapy; tolerance