TY - JOUR
T1 - Identification and analysis of peanut-specific effector T and regulatory T cells in children allergic and tolerant to peanut
AU - Weissler, Katherine A.
AU - Rasooly, Marjohn
AU - DiMaggio, Tom
AU - Bolan, Hyejeong
AU - Cantave, Daly
AU - Martino, David
AU - Neeland, Melanie R.
AU - Tang, Mimi L.K.
AU - Dang, Thanh D.
AU - Allen, Katrina J.
AU - Frischmeyer-Guerrerio, Pamela A.
N1 - Publisher Copyright:
© 2018
PY - 2018/5
Y1 - 2018/5
N2 - Background: Peanut allergy (PA) is potentially life-threatening and generally persists for life. Recent data suggest the skin might be an important route of initial sensitization to peanut, whereas early oral exposure to peanut is protective. In mice regulatory T (Treg) cells are central to the development of food tolerance, but their contribution to the pathogenesis of food allergy in human subjects is less clear. Objective: We sought to quantify and phenotype CD4 + peanut-specific effector T (ps-Teff) cells and peanut-specific regulatory T (ps-Treg) cells in children with and without PA or PS. Methods: ps-Teff and ps-Treg cells were identified from peripheral blood of children with PA, children with PS, and nonsensitized/nonallergic (NA) school-aged children and 1-year-old infants based on upregulation of CD154 or CD137, respectively, after stimulation with peanut extract. Expression of cytokines and homing receptors was evaluated by using flow cytometry. Methylation at the forkhead box protein 3 (FOXP3) locus was measured as a marker of Treg cell stability. Results: Differential upregulation of CD154 and CD137 efficiently distinguished ps-Teff and ps-Treg cells. A greater percentage of ps-Teff cells from infants with PA and infants with PS expressed the skin-homing molecule cutaneous lymphocyte antigen, suggesting activation after exposure through the skin, compared with NA infants. Although ps-Teff cells in both school-aged and infant children with PA produced primarily T H 2 cytokines, a T H 1-skewed antipeanut response was seen only in NA school-aged children. The frequency, homing receptor expression, and stability of ps-Treg cells in infants and school-aged children were similar, regardless of allergic status. Conclusions: Exposure to peanut through the skin can prime the development of T H 2 ps-Teff cells, which promote sensitization to peanut, despite the presence of normal numbers of ps-Treg cells.
AB - Background: Peanut allergy (PA) is potentially life-threatening and generally persists for life. Recent data suggest the skin might be an important route of initial sensitization to peanut, whereas early oral exposure to peanut is protective. In mice regulatory T (Treg) cells are central to the development of food tolerance, but their contribution to the pathogenesis of food allergy in human subjects is less clear. Objective: We sought to quantify and phenotype CD4 + peanut-specific effector T (ps-Teff) cells and peanut-specific regulatory T (ps-Treg) cells in children with and without PA or PS. Methods: ps-Teff and ps-Treg cells were identified from peripheral blood of children with PA, children with PS, and nonsensitized/nonallergic (NA) school-aged children and 1-year-old infants based on upregulation of CD154 or CD137, respectively, after stimulation with peanut extract. Expression of cytokines and homing receptors was evaluated by using flow cytometry. Methylation at the forkhead box protein 3 (FOXP3) locus was measured as a marker of Treg cell stability. Results: Differential upregulation of CD154 and CD137 efficiently distinguished ps-Teff and ps-Treg cells. A greater percentage of ps-Teff cells from infants with PA and infants with PS expressed the skin-homing molecule cutaneous lymphocyte antigen, suggesting activation after exposure through the skin, compared with NA infants. Although ps-Teff cells in both school-aged and infant children with PA produced primarily T H 2 cytokines, a T H 1-skewed antipeanut response was seen only in NA school-aged children. The frequency, homing receptor expression, and stability of ps-Treg cells in infants and school-aged children were similar, regardless of allergic status. Conclusions: Exposure to peanut through the skin can prime the development of T H 2 ps-Teff cells, which promote sensitization to peanut, despite the presence of normal numbers of ps-Treg cells.
KW - CD137
KW - CD154
KW - Peanut allergy
KW - antigen specificity
KW - cutaneous lymphocyte antigen
KW - food allergy
KW - regulatory T
KW - route of sensitization
KW - α4β7
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UR - http://www.scopus.com/inward/citedby.url?scp=85043475589&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2018.01.035
DO - 10.1016/j.jaci.2018.01.035
M3 - Article
C2 - 29454004
AN - SCOPUS:85043475589
SN - 0091-6749
VL - 141
SP - 1699-1710.e7
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -