Background: The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance.
Objective: Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy.
Methods: In a phase 1 single-site study, we studied participants (n = 23) undergoing peanut OIT and compared them with age-matched allergic control subjects (n = 20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n = 7), whereas those who had an allergic reaction were categorized as nontolerant (NT; n = 13).
Results: Antibody and basophil activation measurements did not statistically differentiate between NT versus IT participants. However, T-cell function and demethylation of forkhead box protein 3 (FOXP3) CpG sites in antigen-induced regulatory T cells were significantly different between IT versus NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced regulatory T cells.
Conclusion: In summary, modifications at the DNA level of antigen-induced T-cell subsets might be predictive of a state of operationally defined clinical immune tolerance during peanut OIT.
Keywords: APC; Antigen-induced regulatory T; Antigen-presenting cell; CD40 ligand; CD40L; CFSE; Carboxyfluorescein succinimidyl ester; DBPCFC; DC; Dendritic cell; Double-blind, placebo-controlled food challenge; Effector CD4(+) T; FOXP3; Food allergy; Forkhead box protein 3; IT; Immune tolerant; Induced regulatory T; LAG3; Lymphocyte activation gene 3; MFI; Mean fluorescence intensity; NT; Natural regulatory T; Nonspecific regulatory T; Nontolerant; OFC; OIT; Oral food challenge; Oral immunotherapy; Regulatory T; SPT; Skin prick test; T(R)1; Teff; Treg; Type 1 regulatory T; T regulatory cells; ai-Treg; allergy; desensitization; epigenetics; forkhead box protein 3; iTreg; nTreg; ns-Treg; oral immunotherapy; peanut; tolerance.
Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.