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

• Published in: Clinical and experimental allergy 2015-07, Vol.45 (7), p.1201-1213
• Main Authors: Wisniewski, J. A., Commins, S. P., Agrawal, R., Hulse, K. E., Yu, M. D., Cronin, J., Heymann, P. W., Pomes, A., Platts-Mills, T. A., Workman, L., Woodfolk, J. A.
• Format: Article
• Language: English
• Subjects: 2S Albumins, Plant - immunology; Administration, Oral; Adolescent; Allergens - administration & dosage; Allergens - immunology; Antigens, Plant - administration & dosage; Antigens, Plant - immunology; Ara h 1; Ara h 2; Child; Child, Preschool; cytokines; Cytokines - biosynthesis; Desensitization, Immunologic; Female; Glycoproteins - immunology; Humans; IgE; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunophenotyping; Infant; Interleukin-4 - biosynthesis; Male; oral immunotherapy; peanut allergy; Peanut Hypersensitivity - immunology; Peanut Hypersensitivity - metabolism; Peanut Hypersensitivity - therapy; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th1; Th2; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.12537

Summary 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 kUA/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.