Early regulatory B cell induction and Th/Tr17 responses relates to success of long-term grass-pollen AIT

The up-dosing phase is marked by increased IL-10+B-cells with allergen-specific PD-L1 up-regulation, while effector Th1/Th17 cells and CCR6+IL-17+FoxP3+T-cells decrease. The conversion phase exhibits Th17 recovery in the absence of Th2cells. The tolerance-mounting phase after three years of treatment is characterized by induction of Tregs while Th2 and phleum-specific IL-17A responses decrease. Notably, high ratios of circulating Breg/Th17 following initial AIT correlate significantly with clinical improvement after three years. Our data imply differential shifts in the hierarchy of tolerance in three distinct phases of AIT characterized by conversion of regulatory against pro-inflammatory mechanisms, of which the Breg/Th17 ratio after initial treatment emerges as potential early prediction of AIT efficacy. Nasal brushings were performed in healthy controls in and out of grass pollen season, untreated patients suffering from allergic rhinitis (only in grass pollen season), and allergic rhinitis patients who received allergen-specific immunotherapy (AIT). From treated patients, samples were take before treatment (baseline - T0), 6 hours after last topdose (T4), and after 3 years of completed AIT (T9).