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. 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.
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Authors | J 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 |
Journal | Clinical 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 |
PMID | 25823600
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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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
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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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