Identification and analysis of peanut-specific T effector and T regulatory cells in children allergic and tolerant to peanut

Publication date: Available online 15 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Katherine A. Weissler, Marjohn Rasooly, Tom DiMaggio, Hyejeong Bolan, Daly Cantave, David Martino, Melanie R. Neeland, Mimi LK. Tang, Thanh D. Dang, Katrina J. Allen, Pamela A. Frischmeyer-Guerrerio
BackgroundPeanut allergy is potentially life-threatening and generally persists lifelong. Recent data suggests the skin may be an important route of initial sensitization to peanut, while early oral exposure to peanut is protective. In mice, T regulatory cells (Tregs) are central to development of tolerance to food, but their contribution to the pathogenesis of food allergy in humans is less clear.ObjectiveWe sought to quantify and phenotype peanut-specific CD4+ T effector (ps-Teff) and ps-Tregs in children with and without peanut allergy or sensitization.MethodsPs-Teffs and ps-Tregs were identified from peripheral blood of peanut allergic, peanut sensitized, and non-sensitized/non-allergic school-aged children and one year old infants based on upregulation of CD154 or CD137, respectively, following stimulation with peanut extract. Expression of cytokines and homing receptors were evaluated using flow cytometry. Methylation at the FOXP3 locus was measured as a marker of Treg stability.ResultsDifferential upregulation of CD154 and CD137 efficiently distinguished ps-Teffs and ps-Tregs. A greater percentage of ps-Teffs from peanut allergic and sensitized infants expressed the skin homing molecule CLA, suggesting activation following exposure through the skin, compared to non-allergic infants. While ps-Teffs in both school-aged and infant peanut-allergic children produced primarily Th2 cytokines, a Th1-skewed anti-peanut response was only seen in non-allergic school-aged children. The frequency, homing receptor expression, and stability of ps-Tregs in infant and school-aged children were similar regardless of allergic status.ConclusionsExposure to peanut through the skin may prime the development of Th2 ps-Teffs that promote sensitization to peanut, despite the presence of normal numbers of ps-Tregs.

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