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Naturally occurring tolerance acquisition to foods in previously allergic children is characterized by antigen specificity and associated with increased subsets of regulatory T cells
Author(s) -
Qamar N.,
Fishbein A. B.,
Erickson K. A.,
Cai M.,
Szychlinski C.,
Bryce P. J.,
Schleimer R. P.,
Fuleihan R. L.,
Singh A. M.
Publication year - 2015
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12570
Subject(s) - foxp3 , il 2 receptor , antigen , immunology , peripheral blood mononuclear cell , interleukin 7 receptor , allergy , cd19 , medicine , cd3 , stimulation , biology , immune system , t cell , cd8 , in vitro , biochemistry
Summary Background Food allergy affects approximately 6–8% of children, and increasing in prevalence. Some children naturally outgrow their food allergy without intervention, but the mechanisms by which this occurs remain poorly understood. We sought to investigate the role of regulatory T cells in the development of naturally acquired tolerance. Methods Fifty‐eight children (1–18 years) with either egg or peanut allergy, recent acquisition of natural tolerance to egg or peanut, or no food allergy were studied. Peripheral blood mononuclear cells ( PBMC ) from these groups were stimulated with relevant antigen for 48 h and flow cytometry performed to characterize both surface ( CD 3, CD 4, CD 25, CD 14, CD 19, and CD 127) and intracellular markers ( IL ‐10, Foxp3, and IL ‐5). Results Resting PBMC from naturally tolerant patients had significantly increased CD 3+ CD 4+ CD 25+ CD 127loFoxp3+ cells, when compared to allergic or control patients (mean 6.36 vs. 2.37 vs. 2.62%, respectively, P < 0.05). Upon stimulation with relevant antigen, naturally tolerant patients also had increased IL ‐10‐expressing CD 25+ CD 127lo cells (6.33 vs. 1.65 vs. 0.7, P < 0.01), Foxp3+ cells (mean 12.6 vs. 5.42 vs. 3%, P < 0.01), and CD 4+ cells (mean 4.48 vs. 1.59 vs. 0.87%, P < 0.01); the increase was not observed in PBMC s from allergic or control patients. Additionally, this upregulation was only seen with relevant antigen stimulation and not upon stimulation with unrelated antigen. Conclusion The increased CD 3+ CD 4+ CD 25+ CD 127lo cells at baseline and upon stimulation and increased induction of IL ‐10‐producing cells of several types, including Tr1 cells, from naturally tolerant patients suggests an important role for regulatory T cell subsets in the acquisition of natural tolerance.