Understanding the mechanisms of allergen-specific immune modulation in nonallergic individuals is key to recapitulate immune tolerance and to develop novel allergy treatments. Herein, we characterized mouse-specific T cell responses in nonallergic laboratory animal-care workers before and after reexposure to mice. PBMCs were collected and stimulated with developed peptide pools identified from high-molecular-weight fractions of mouse allergen extracts. Sizable CD4 T cell responses were noted and were temporarily decreased in most subjects upon reexposure, with the magnitude of decrease positively correlated with time of reexposure but not the duration of the break. Interestingly, the suppression was specific to mouse allergens without affecting responses of bystander antigens. Further, PBMC fractioning studies illustrated that the modulation is unlikely from T cells, while B cell depletion and exchange reversed the suppression of responses, suggesting that B cells may be the key modulators. Increased levels of regulatory cytokines (IL-10 and TGF-β1) in the cell culture supernatant and plasma mouse-specific IgG4 were also observed after reexposure, consistent with B cell–mediated modulation mechanisms. Overall, these results suggest that nonallergic status is achieved by an active, time-related, allergen-specific, B cell-dependent regulatory process upon reexposure, the mechanisms of which should be detailed by further molecular studies.
Esther Dawen Yu, Luise Westernberg, Alba Grifoni, April Frazier, Aaron Sutherland, Eric Wang, Bjoern Peters, Ricardo da Silva Antunes, Alessandro Sette