IFN-ă Induces Milk Allergen-Specific IL-10-Producing Regulatory B Cells in Non -IgE Mediated Milk Allergy

Background: Tolerance induction is one of the most important concerns in the treatment of allergies and autoimmune diseases. L-10-producing regulatory B cells (Br1s) seem to have a role in immune tolerance to food allergens. Oral immunotherapy using IFN-gamma has been successful for food allergy treatmen. We were to investigate the effects of IFN-gamma on allergen-specific Br1 responses in milk allergy patients and milk-tolerant subjects to evaluate the mmunomodulatory effects of IFN-gamma on Br1 cell responses.

Methods: The six milk allergy patients and eight milk-tolerant subjects were selected by DBPCFC and clinical characteristics. The PBMCs were stimulated  in vitro with casein only, IFN-gamma with casein, or without any stimulant. And the CD19(+)CD5(+) B cells were gated and the expression of IL-10 and Annexin V binding were subsequently analysed

Results: In milk allergy group, the Br1 fraction decreased from 24.4% to 15.0% (p=0.002) after casein stimulation and it was recovered to 22.6% in the presence of IFN-gamma ( p=0.006). In milk-tolerant group, the Br1 fraction increased from 9.4% to 17.1% after casein stimulation (p=0.014) and to 15.7% after  IFN-gamma were added ( p=0.066). The proportion of apoptotic Br1s among CD5(+) B cells decreased from 16.5% to 8.1% with casein (p=0.003) and to 11.8% with IFN-gamma and casein (p=0.141) in milk allergy group, while in milk-tolerant group, the proportion of apoptotic Br1 increased from 8.2% to 15.0% after casein stimulation( p=0.014), but was unchanged by casein with IFN-gamma.

Conclusions: Allergen-specific Br1 responses and the apoptotic Br1 fraction were induced by IFN-gamma in milk allergy patients, but were not changed in milk-tolerant subjects. Finally IFN-gamma induced allergen-specific Br1 responses and immune tolerance to specific allergens in milk allergy patients,.