Katherine A Weissler1, Marjohn Rasooly1, Tom DiMaggio1, Hyejeong Bolan1, Daly Cantave1, David Martino2, Melanie R Neeland3, Mimi L K Tang4, Thanh D Dang2, Katrina J Allen4, Pamela A Frischmeyer-Guerrerio5. 1. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Md. 2. Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia; Department of Pediatrics, University of Melbourne, Melbourne, Australia. 3. Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia. 4. Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia; Department of Pediatrics, University of Melbourne, Melbourne, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Melbourne, Australia. 5. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Md. Electronic address: pamela.guerrerio@nih.gov.
Abstract
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 TH2 cytokines, a TH1-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 TH2 ps-Teff cells, which promote sensitization to peanut, despite the presence of normal numbers of ps-Treg cells. Published by Elsevier Inc.
BACKGROUND:Peanutallergy (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 infantchildren with PA produced primarily TH2 cytokines, a TH1-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 TH2 ps-Teff cells, which promote sensitization to peanut, despite the presence of normal numbers of ps-Treg cells. Published by Elsevier Inc.
Authors: S E Ashley; H-T T Tan; P Vuillermin; S C Dharmage; M L K Tang; J Koplin; L C Gurrin; A Lowe; C Lodge; A-L Ponsonby; J Molloy; P Martin; M C Matheson; R Saffery; K J Allen; J A Ellis; D Martino Journal: Allergy Date: 2017-04-04 Impact factor: 13.146
Authors: Karen S Tuano; Jordan S Orange; Kathleen Sullivan; Charlotte Cunningham-Rundles; Francisco A Bonilla; Carla M Davis Journal: J Allergy Clin Immunol Date: 2014-11-25 Impact factor: 10.793
Authors: Jennifer J Koplin; Melissa Wake; Shyamali C Dharmage; Melanie Matheson; Mimi L K Tang; Lyle C Gurrin; Terry Dwyer; Rachel L Peters; Susan Prescott; Anne-Louise Ponsonby; Adrian J Lowe; Katrina J Allen Journal: Int J Epidemiol Date: 2015-01-21 Impact factor: 7.196
Authors: H Bernard; S Ah-Leung; M-F Drumare; C Feraudet-Tarisse; V Verhasselt; J-M Wal; C Créminon; K Adel-Patient Journal: Allergy Date: 2014-04-29 Impact factor: 13.146
Authors: Wayne G Shreffler; Niya Wanich; Marla Moloney; Anna Nowak-Wegrzyn; Hugh A Sampson Journal: J Allergy Clin Immunol Date: 2009-01 Impact factor: 10.793
Authors: Udo Baron; Stefan Floess; Georg Wieczorek; Katrin Baumann; Andreas Grützkau; Jun Dong; Andreas Thiel; Tina J Boeld; Petra Hoffmann; Matthias Edinger; Ivana Türbachova; Alf Hamann; Sven Olek; Jochen Huehn Journal: Eur J Immunol Date: 2007-09 Impact factor: 5.532
Authors: Helen A Brough; Andrew H Liu; Scott Sicherer; Kerry Makinson; Abdel Douiri; Sara J Brown; Alick C Stephens; W H Irwin McLean; Victor Turcanu; Robert A Wood; Stacie M Jones; Wesley Burks; Peter Dawson; Donald Stablein; Hugh Sampson; Gideon Lack Journal: J Allergy Clin Immunol Date: 2014-11-18 Impact factor: 10.793
Authors: Ye Zheng; Steven Josefowicz; Ashutosh Chaudhry; Xiao P Peng; Katherine Forbush; Alexander Y Rudensky Journal: Nature Date: 2010-01-13 Impact factor: 49.962
Authors: M Cecilia Berin; Charuta Agashe; A Wesley Burks; David Chiang; Wendy F Davidson; Peter Dawson; Alexander Grishin; Alice K Henning; Stacie M Jones; Edwin H Kim; Donald Y M Leung; Madhan Masilamani; Amy M Scurlock; Scott H Sicherer; Robert A Wood; Hugh A Sampson Journal: J Allergy Clin Immunol Date: 2021-10-13 Impact factor: 14.290
Authors: Bert Ruiter; Neal P Smith; Brinda Monian; Ang A Tu; Elizabeth Fleming; Yamini V Virkud; Sarita U Patil; Charles A Whittaker; J Christopher Love; Wayne G Shreffler Journal: J Allergy Clin Immunol Date: 2019-10-22 Impact factor: 10.793
Authors: Rebecca Czolk; Julia Klueber; Martin Sørensen; Paul Wilmes; Françoise Codreanu-Morel; Per Stahl Skov; Christiane Hilger; Carsten Bindslev-Jensen; Markus Ollert; Annette Kuehn Journal: Front Immunol Date: 2021-01-28 Impact factor: 7.561
Authors: Brinda Monian; Ang A Tu; Bert Ruiter; Duncan M Morgan; Patrick M Petrossian; Neal P Smith; Todd M Gierahn; Julia H Ginder; Wayne G Shreffler; J Christopher Love Journal: J Clin Invest Date: 2022-01-18 Impact factor: 14.808
Authors: Helen A Brough; Kari C Nadeau; Sayantani B Sindher; Shifaa S Alkotob; Susan Chan; Henry T Bahnson; Donald Y M Leung; Gideon Lack Journal: Allergy Date: 2020-05-18 Impact factor: 13.146