title: Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy.
abstract: BACKGROUND
  Only limited evidence is available regarding the cytokine repertoire of effector T cells associated with peanut allergy, and how these responses relate to IgE antibodies to peanut components.
  
  
  OBJECTIVE
  To interrogate T cell effector cytokine populations induced by Ara h 1 and Ara h 2 among peanut allergic (PA) children in the context of IgE and to evaluate their modulation during oral immunotherapy (OIT).
  
  
  METHODS
  Peanut-reactive effector T cells were analysed in conjunction with specific IgE profiles in PA children using intracellular staining and multiplex assay. Cytokine-expressing T cell subpopulations were visualized using SPICE.
  
  
  RESULTS
  Ara h 2 dominated the antibody response to peanut as judged by prevalence and quantity among a cohort of children with IgE to peanut. High IgE (> 15 kU(A)/L) was almost exclusively associated with dual sensitization to Ara h 1 and Ara h 2 and was age independent. Among PA children, IL-4-biased responses to both major allergens were induced, regardless of whether IgE antibodies to Ara h 1 were present. Among subjects receiving OIT in whom high IgE was maintained, Th2 reactivity to peanut components persisted despite clinical desensitization and modulation of allergen-specific immune parameters including augmented specific IgG4 antibodies, Th1 skewing and enhanced IL-10. The complexity of cytokine-positive subpopulations within peanut-reactive IL-4(+) and IFN-γ(+) T cells was similar to that observed in those who received no OIT, but was modified with extended therapy. Nonetheless, high Foxp3 expression was a distinguishing feature of peanut-reactive IL-4(+) T cells irrespective of OIT, and a correlate of their ability to secrete type 2 cytokines.
  
  
  CONCLUSIONS
  Although total numbers of peanut-reactive IL-4(+) and IFN-γ(+) T cells are modulated by OIT in highly allergic children, complex T cell populations with pathogenic potential persist in the presence of recognized immune markers of successful immunotherapy.
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.|Department of Pediatrics, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Wisniewski
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.|Department of Pediatrics, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Commins
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Agrawal
authors.affiliation: Division of Allergy-Immunology, Feinberg School of Medicine Northwestern University, Chicago, IL, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Hulse
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Yu
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Cronin
authors.affiliation: Department of Pediatrics, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Heymann
authors.affiliation: Indoor Biotechnologies Inc., Charlottesville, VA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pomes
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Platts-Mills
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Workman
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Woodfolk
mesh_terms: D055516:2S Albumins, Plant / Q000276:immunology; D000284:Administration, Oral; D000293:Adolescent; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis*; D003888:Desensitization, Immunologic; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D007223:Infant; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D021183:Peanut Hypersensitivity / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D055516:2S Albumins, Plant; D000485:Allergens; D052179:Antigens, Plant; C500890:Ara h 2 allergen, Arachis hypogaea; D016207:Cytokines; D006023:Glycoproteins; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E
keywords: Ara h 1; Ara h 2; IgE; Th1; Th2; cytokines; oral immunotherapy; peanut allergy
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