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

J. A. Wisniewski, S. P. Commins, R. Agrawal, Kathryn E Hulse, M. D. Yu, J. Cronin, P. W. Heymann, A. Pomes, T. A. Platts-Mills, L. Workman, J. A. Woodfolk*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1201-1213
Number of pages13
JournalClinical and Experimental Allergy
Volume45
Issue number7
DOIs
StatePublished - Jan 1 2015

Fingerprint

Immunotherapy
Cytokines
T-Lymphocytes
Immunoglobulin E
Interleukin-4
Allergens
Antibodies
Arachis
Peanut Hypersensitivity
Interleukin-10
Population
Antibody Formation
Immunoglobulin G
Biomarkers
Staining and Labeling

Keywords

  • Ara h 1
  • Ara h 2
  • Cytokines
  • IgE
  • Oral immunotherapy
  • Peanut allergy
  • Th1
  • Th2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Wisniewski, J. A. ; Commins, S. P. ; Agrawal, R. ; Hulse, Kathryn E ; Yu, M. D. ; Cronin, J. ; Heymann, P. W. ; Pomes, A. ; Platts-Mills, T. A. ; Workman, L. ; Woodfolk, J. A. / Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy. In: Clinical and Experimental Allergy. 2015 ; Vol. 45, No. 7. pp. 1201-1213.
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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 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.",
keywords = "Ara h 1, Ara h 2, Cytokines, IgE, Oral immunotherapy, Peanut allergy, Th1, Th2",
author = "Wisniewski, {J. A.} and Commins, {S. P.} and R. Agrawal and Hulse, {Kathryn E} and Yu, {M. D.} and J. Cronin and Heymann, {P. W.} and A. Pomes and Platts-Mills, {T. A.} and L. Workman and Woodfolk, {J. A.}",
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Wisniewski, JA, Commins, SP, Agrawal, R, Hulse, KE, Yu, MD, Cronin, J, Heymann, PW, Pomes, A, Platts-Mills, TA, Workman, L & Woodfolk, JA 2015, 'Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy', Clinical and Experimental Allergy, vol. 45, no. 7, pp. 1201-1213. https://doi.org/10.1111/cea.12537

Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy. / Wisniewski, J. A.; Commins, S. P.; Agrawal, R.; Hulse, Kathryn E; Yu, M. D.; Cronin, J.; Heymann, P. W.; Pomes, A.; Platts-Mills, T. A.; Workman, L.; Woodfolk, J. A.

In: Clinical and Experimental Allergy, Vol. 45, No. 7, 01.01.2015, p. 1201-1213.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy

AU - Wisniewski, J. A.

AU - Commins, S. P.

AU - Agrawal, R.

AU - Hulse, Kathryn E

AU - Yu, M. D.

AU - Cronin, J.

AU - Heymann, P. W.

AU - Pomes, A.

AU - Platts-Mills, T. A.

AU - Workman, L.

AU - Woodfolk, J. A.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Ara h 1

KW - Ara h 2

KW - Cytokines

KW - IgE

KW - Oral immunotherapy

KW - Peanut allergy

KW - Th1

KW - Th2

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SN - 0954-7894

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