ABSTRACT
Peanut allergy is considered to be the most common cause for food-induced anaphylaxis. Currently, no approved treatment is available. Avoidance is the only measure to prevent anaphylactic reactions to peanuts. T-helper cells are of special importance for the sensitization process and the maintenance of allergic inflammation. Identifying markers of allergen-specific T-cell responses may help to develop novel treatment approaches. Therefore, we aimed to define new T-cell target genes in Ara h 2-specific T cells and to investigate the possibility of using them as biomarkers of peanut allergy in peripheral blood mononuclear cells (PBMCs). We performed whole mRNA array analysis (whole human genome oligo microarray) of in vitro expanded Ara h 2-specific T cells (CFSElowCD3+CD4+) from 5 peanut-allergic (PA) and 5 non-peanut-sensitized individuals. Expression of selected genes as a result of a two-step bioinformatic approach was confirmed in a second cohort by quantitative PCR. TGF-ß- activated kinase 1 and MAP3K7 binding protein 3 (TAB3), calcium/calmodulin-dependent protein kinase type IV (CAMK4) and HemK methyltransferase family member 1 (HEMK1) were significantly upregulated in Ara h 2-specific T cells of PA patients. In addition, the expression of these genes was also assessed in unstimulated PBMCs from a cohort (n = 43) of PA, atopic non-PA, and nonatopic controls. Interestingly, in unstimulated PBMCs, TAB3 expression was significantly downregulated in PA patients compared to atopic non-PA individuals. Thus, TAB3 may play a significant role at the level of T-cell activation and may also be a candidate biomarker for PA.
Subject(s)
2S Albumins, Plant/immunology , Adaptor Proteins, Signal Transducing/physiology , Antigens, Plant/immunology , Arachis/immunology , CD4-Positive T-Lymphocytes/immunology , Glycoproteins/immunology , Peanut Hypersensitivity/etiology , Adolescent , Cells, Cultured , Child , Female , Humans , Lymphocyte Activation , Male , Methyltransferases/physiology , NF-kappa B/physiologySubject(s)
2S Albumins, Plant/chemistry , Antigens, Plant/chemistry , 2S Albumins, Plant/immunology , Adolescent , Adult , Amino Acid Sequence , Antigens, Plant/immunology , Arachis/immunology , Child , Child, Preschool , Cytokines/immunology , Desensitization, Immunologic , Female , Humans , Immunoglobulin E/immunology , Male , Protein Conformation , Protein Engineering , T-Lymphocytes/immunology , Young AdultABSTRACT
Food allergy is the major reason for severe anaphylaxis in childhood and adolescence. Currently, effective and safe treatments for food allergy are unavailable. Allergen-specific CD4+ T cells have a pivotal role in causing and maintaining the allergic response to food allergens. The purpose of this review is to provide an overview on the role of allergen-specific T cells in food allergy during allergic sensitization, natural tolerance development and allergen immunotherapy. Allergen-specific T cells in the context of food allergy are predominantly of a Th2 type with slightly different surface marker expression patterns in different food allergies. During the process of reverting food allergy to a status of tolerance or sustained unresponsiveness there is a loss of this Th2 committed compartment with an asymptotic approximation to a regulatory and Th0/Th1 dominated compartment seen in non-allergic individuals. This process is accompanied by a significant reduction of absolute frequencies of allergen-specific T cells. Particularly, regulatory T cells may provide significant help to achieve sustained control of the effector cell populations via suppression of effector cell function and possibly induction of blocking antibodies.
