Allergy Asthma Immunol Res.  2013 Jan;5(1):48-54. 10.4168/aair.2013.5.1.48.

In Vitro Induction of Allergen-Specific Interleukin-10-Producing Regulatory B Cell Responses by Interferon-gamma in Non-Immunoglobulin E-Mediated Milk Allergy

• Lee SJ
• Noh G
• Lee JH

• KMID: 2167006
• DOI: http://doi.org/10.4168/aair.2013.5.1.48

Abstract

PURPOSE
Specific oral immunotherapy (SOIT) using interferon-gamma (IFN-gamma) 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-gamma 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-gamma 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-gamma and analyzed by flow cytometry.
RESULTS
IFN-gamma had no effect on total cell counts or the proportion of Br1 cells in PBMCs. IFN-gamma 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-gamma + casein stimulated cells, and the Br1 fractions were decreased after casein stimulation and recovered in the addition of IFN-gamma for stimulation. In the milk-tolerant group, Br1 counts increased in the casein stimulated cells and in the IFN-gamma + casein stimulated cells, but the increase was significantly less when IFN-gamma was added, and the Br1 fractions were increased after casein stimulation and IFN-gamma + casein stimulation, that was not significant when IFN-gamma was added.
CONCLUSIONS
IFN-gamma-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.

Keyword

Atopic dermatitis; IFN-gamma; IL-10-producing regulatory B cell; non-IgE-mediated milk allergy; oral immunotherapy; tolerance

MeSH Terms

Allergens
B-Lymphocytes
B-Lymphocytes, Regulatory
Caseins
Cell Count
Dermatitis, Atopic
Food Hypersensitivity
Humans
Immune Tolerance
Immunotherapy
Interferon-gamma
Interleukin-10
Milk
Milk Hypersensitivity
Allergens
Caseins
Interferon-gamma
Interleukin-10

Figure

• 

  Fig. 1 Non-specific effects of interferon-γ (IFN-γ) on interleukin-10 (IL-10)-producing regulatory B cell (Br1) responses in peripheral blood mononuclear cells (PBMCs). (A) Gating of CD19(+)CD5(+) B cells and subgating of IL-10-producing regulatory B cells. (B) Representative plot of IL-10-producing regulatory B cell (Br1) responses induced by IFN-γ simulation of PBMCs from milk allergy and milk-tolerant subjects. Numbers indicate the percentage of cells. (C) Changes in Br1 cell numbers caused by IFN-γ in milk allergy patients and milk-tolerant subjects. (D) Changes in the proportion of Br1 cells to CD5(+) B cells as a result of IFN-γ treatment. Positive, milk allergy patient (DBPCFC positive); Negative, milk-tolerant subject (DBPCFC negative); None, unstimulated PBMCs.

• 

  Fig. 2 Immunomodulatory effects of interferon-γ (IFN-γ) on allergen-specific interleukin-10 (IL-10)-producing regulatory B cell (Br1) responses in peripheral blood mononuclear cells (PBMCs). (A) Representative plot of allergen-specific Br1 responses of cells from milk allergy patients and milk-tolerant subjects induced by stimulation with casein and/or IFN-γ. Numbers indicate the percentage of cells. (B) Allergen-specific changes in Br1 cell numbers in milk allergy patients and milk-tolerant subjects. (C) Changes in the proportion of Br1 cells to CD5(+) B cells as a result of IFN-γ treatment. Positive, milk allergy patient (DBPCFC positive); Negative, milk-tolerant subject (DBPCFC negative); None, unstimulated PBMCs; Casein, PBMCs stimulated with casein; IFN+Casein, PBMCs stimulated with IFN-γ and casein simultaneously.

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