Immune tolerance is defined as nonresponsiveness of the adaptive immune system to antigens. Immune mechanisms preventing inappropriate immune reactivity to innocuous antigens include deletion of reactive lymphocytes and generation of regulatory T (Treg) cells. The normal response to food antigens is the generation of antigen-specific Treg cells. In patients with food allergy, the dominant immune response is a T(H)2-skewed T-cell response and the generation of food-specific IgE antibodies from B cells. It is not known whether a failure of the Treg cell response is behind this inappropriate immune response, but interventions that boost the Treg cell response, such as mucosal immunotherapy, might lead to a restoration of immune tolerance to foods. Tolerance has been notoriously difficult to restore in animal disease models, but limited data from human trials suggest that tolerance (sustained nonresponsiveness) can be re-established in a subset of patients. Furthermore, studies on the natural history of food allergy indicate that spontaneous development of tolerance to foods over time is not uncommon. The current challenge is to understand the mechanisms responsible for restoration of natural or induced tolerance so that interventions can be developed to more successfully induce tolerance in the majority of patients with food allergy.
[Show abstract][Hide abstract] ABSTRACT: Cow's milk allergy (CMA) continues to be a growing health concern for infants living in Western countries. The long-term prognosis for the majority of affected infants is good, with about 80% naturally acquiring tolerance by the age of four years. However, recent studies suggest that the natural history of CMA is changing, with an increasing persistence until later ages. The pathogenesis of CMA, as well as oral tolerance, is complex and not completely known, although numerous studies implicate gut-associated immunity and enteric microflora, and it has been suggested that an altered composition of intestinal microflora results in an unbalanced local and systemic immune response to food allergens. In addition, there are qualitative and quantitative differences in the composition of gut microbiota between patients affected by CMA and healthy infants. These findings prompt the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, could restore intestinal homeostasis and prevent or alleviate allergy, at least in part by interacting with the intestinal immune cells. The aim of this paper is to review what is currently known about the use of probiotics as dietary supplements in CMA.
[Show abstract][Hide abstract] ABSTRACT: The mechanism of antigen specific immunotherapy (ASIT) remains to be further understood. The present study aims to investigate the role of ASIT in the generation of tolerogenic dendritic cells (DC) in patients with food allergy (FA).
Twenty patients with egg FA and 10 healthy subjects were recruited into this study. Blood samples were obtained from each subject before and after the ASIT and analyzed by flow cytometry.
In FA patients, the frequencies of CD27(+) B cells and TGF-b(+) DCs were significantly lower than that in healthy subjects. More than 90% CD27(+) B cells also express CD35; about 90% CD27(+) CD35(+) B cells expressed TGF-b. Coculture of CD27(+) CD35(+) B cells with immature DCs generated TGF-b-expressing tolerogenic DCs; the latter was able to induce CD4(+) CD25(+) Foxp3(+) regulatory T cells.
Treatment with ASIT can induce TGF-b-expressing tolerogenic DCs in patients with FA.
[Show abstract][Hide abstract] ABSTRACT: Shellfish allergy is an immune-mediated adverse reaction to allergenic shellfish and is responsible for significant morbidity and mortality. CD4 T cell responses play an important role in the pathophysiological mechanisms of sensitization and in production of IgE.
We sought to identify and validate CD4 T cell shrimp tropomyosin-derived epitopes and characterize CD4 T cell responses in subjects with a clinical history of shellfish allergy.
Using an in vitro MHC-peptide binding assay, we screened 91 overlapping peptides and identified 28 epitopes with moderate and strong binding capacities; 3 additional peptides were included based on MHC binding prediction score. These peptides were then examined in proliferation and cytokine release assays with T cells from allergic subjects.
17 epitopes restricted to DRB∗01:01, DRB1∗03:01, DRB1∗04:01, DRB1∗09:01, DQB1∗02:01, DQB1∗03:02 and DQB1∗05:01 alleles were identified and validated by both the MHC binding and the functional assays. Two peptides showed specificities to more than one MHC class II allele. We demonstrated that these peptides exert functional responses in an epitope specific manner, eliciting predominantly IL-6 and IL-13.
The identified epitopes are specific to common MHC class II alleles in the general population. Our study provides important data for the design of peptide-based immunotherapy of shrimp-allergic patients.
Human immunology 08/2013; 33(3). DOI:10.1016/j.humimm.2013.08.276 · 2.14 Impact Factor
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