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Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsJ A Wisniewski, S P Commins, R Agrawal, K E Hulse, M D Yu, J Cronin, P W Heymann, A Pomes, T A Platts-Mills, L Workman, J A Woodfolk
JournalClinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 45 Issue 7 Pg. 1201-13 (Jul 2015) ISSN: 1365-2222 [Electronic] England
PMID25823600 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2015 John Wiley & Sons Ltd.
Chemical References
  • 2S Albumins, Plant
  • Allergens
  • Antigens, Plant
  • Ara h 2 allergen, Arachis hypogaea
  • Cytokines
  • Glycoproteins
  • Immunoglobulin G
  • Interleukin-4
  • Immunoglobulin E
Topics
  • 2S Albumins, Plant (immunology)
  • Administration, Oral
  • Adolescent
  • Allergens (administration & dosage, immunology)
  • Antigens, Plant (administration & dosage, immunology)
  • Child
  • Child, Preschool
  • Cytokines (biosynthesis)
  • Desensitization, Immunologic
  • Female
  • Glycoproteins (immunology)
  • Humans
  • Immunoglobulin E (blood, immunology)
  • Immunoglobulin G (blood, immunology)
  • Immunophenotyping
  • Infant
  • Interleukin-4 (biosynthesis)
  • Male
  • Peanut Hypersensitivity (immunology, metabolism, therapy)
  • T-Lymphocyte Subsets (immunology, metabolism)
  • Th2 Cells (immunology, metabolism)

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