Induction of bystander tolerance and immune deviation following Fel d 1 Peptide Immunotherapy

Publication date: Available online 12 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Daniel M. Moldaver, Mantej S. Bharhani, Christopher D. Rudulier, Jennifer Wattie, Mark D. Inman, Mark Larché
BackgroundTreatment of cat allergic subjects with peptides derived from Fel d 1 (the major cat allergen) ameliorated symptoms of cat allergy in phase 2 clinical trials.ObjectiveTo demonstrate that the tolerance induced by Fel d 1 peptide immunotherapy can be exploited to reduce allergic responses to a second allergen, ovalbumin (OVA), in mice dually sensitized to OVA and Fel d 1.MethodsThe induction of tolerance to OVA was achieved via a simultaneous exposure to both allergens following peptide treatment. Functional tolerance to each allergen was assessed in a model of allergic airways disease, wherein treated mice were protected from eosinophilia, goblet cell hyperplasia and Th2 cellular infiltration.ResultsSuppression of allergic responses to cat allergen challenge was associated with significant increases in CD4+CD25+Foxp3+ T cells, IL-10+ cells and CD19+IL-10+ B cells, whereas the response to OVA was associated with a marked reduction of Th2 cytokine-secreting T cells and less prominent changes in outcomes associated with immune regulation.ConclusionsThese observations suggest that immune tolerance induced by peptide immunotherapy can be used experimentally to treat an allergic response to another allergen, and that the molecular mechanisms underlying the induction of tolerance to a treatment-specific allergen and a bystander allergen may be different.

Graphical abstract

Teaser

Allergen immunotherapy is generally considered to be antigen-specific. Here we show that treatment with components of one allergen can be manipulated to induce functional tolerance to a second allergen, through subtly different mechanisms.


https://ift.tt/2LIDQi3