NIH Research Festival
Food allergies can dramatically affect quality of life and in severe cases result in fatal anaphylactic reactions, particularly in response to peanut. Regulatory T cells are known to be involved in establishing tolerance to ingested foods, but whether defects in regulatory T cells are a major cause of food allergy in the general population remains unclear. Recent studies have suggested that exposure to food antigens through the skin may increase the risk of sensitization and allergy. Efforts to understand the T cell response to food allergens have thus far been impeded by difficulties in identifying cells with T cell receptors that recognize these allergens. We have used a novel technique to identify peanut-specific CD4+ effector and regulatory T cells in peripheral blood based on differential upregulation of CD154 and CD137, respectively, following exposure to peanut extract. In two groups of children, one school-aged and one at one year of age, the frequencies of peanut-specific effector and regulatory T cells were similar between peanut allergic, sensitized, and tolerant children. No differences were found in peanut-specific regulatory T cell suppressive function, stability, or expression of homing receptors between allergic and non-allergic children, which suggests that disparities in regulatory T cells may not be a determining factor in the development of peanut allergy. Peanut-specific effector T cells from peanut allergic children in both age groups were more likely to produce the Th2-associated cytokine IL-13 in response to peanut antigen, while in school-aged non-allergic children, more peanut-specific T cells produced the Th1 cytokine IFN-. Furthermore, peanut-specific effector T cells from one-year old infants with peanut allergy or sensitivity were more likely to express the skin-homing receptor CLA and less likely to express the gut-homing receptor 47 than peanut-specific cells from non-allergic infants. Expression of homing receptors generally reflects the site of initial activation of the T cell; thus this observation indicates that peanut-specific effector T cells from peanut allergic and sensitized infants initially encountered peanut antigen following cutaneous exposure, and supports the theory that exposure to food antigen through the skin, as opposed to oral exposure, in young children can increase the chance of sensitization. A better understanding of allergen-specific T cell responses may inform future treatments of food allergy.
Scientific Focus Area: Immunology
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