Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired

L Pellerin, JA Jenks, S Chinthrajah, T Dominguez, W Block, X Zhou, A Noshirvan, S Gregori, MG Roncarolo, KC Nadeau, R Bacchetta

Research output: Contribution to journalArticle

Abstract

Background: Peanut allergy (PA) is a life-threatening condition that lacks regulator-approved treatment. Regulatory T type 1 (T R 1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro by using tolerogenic dendritic cells. Whether oral immunotherapy (OIT) leads to antigen-specific T R 1 cell induction has not been established. Objectives: We sought to determine whether peanut-specific T R 1 cells can be generated in vitro from peripheral blood of patients with PA at baseline or during OIT and whether they are functional compared with peanut-specific T R 1 cells induced from healthy control (HC) subjects. Methods: Tolerogenic dendritic cells were differentiated in the presence of IL-10 from PBMCs of patients with PA and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h 1 and 2, and used as antigen-presenting cells for autologous CD4 + T cells (CD4 + T cells coincubated with tolerogenic dendritic cells pulsed with the main peanut allergens [pea-T10 cells]). Pea-T10 cells were characterized by the presence of CD49b + lymphocyte-activation gene 3 (LAG3) + T R 1 cells, antigen-specific proliferative responses, and cytokine production. Results: CD49b + LAG3 + T R 1 cells were induced in pea-T10 cells at comparable percentages from HC subjects and patients with PA. Despite their antigen specificity, pea-T10 cells of patients with PA with or without OIT, as compared with those of HC subjects, were not anergic and had high T H 2 cytokine production upon peanut-specific restimulation. Conclusions: Peanut-specific T R 1 cells can be induced from HC subjects and patients with PA, but those from patients with PA are functionally defective independent of OIT. The unfavorable T R 1/T H 2 ratio is discussed as a possible cause of PA T R 1 cell impairment. © 2017 American Academy of Allergy, Asthma & Immunology.
Original languageEnglish
Pages (from-to)202-213.e8
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number1
DOIs
Publication statusPublished - 2018

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Regulatory T-Lymphocytes
Peanut Hypersensitivity
Peas
Healthy Volunteers
Immunotherapy
Dendritic Cells
Lymphocyte Activation
Antigens
In Vitro Techniques
Arachis
Cytokines
T-Lymphocytes
Viral Tumor Antigens
Antigen-Presenting Cells
Allergy and Immunology
Interleukin-10
Allergens
Genes
Hypersensitivity
Asthma

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Pellerin, L., Jenks, JA., Chinthrajah, S., Dominguez, T., Block, W., Zhou, X., ... Bacchetta, R. (2018). Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired. Journal of Allergy and Clinical Immunology, 141(1), 202-213.e8. https://doi.org/10.1016/j.jaci.2017.05.045

Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired. / Pellerin, L; Jenks, JA; Chinthrajah, S; Dominguez, T; Block, W; Zhou, X; Noshirvan, A; Gregori, S; Roncarolo, MG; Nadeau, KC; Bacchetta, R.

In: Journal of Allergy and Clinical Immunology, Vol. 141, No. 1, 2018, p. 202-213.e8.

Research output: Contribution to journalArticle

Pellerin, L, Jenks, JA, Chinthrajah, S, Dominguez, T, Block, W, Zhou, X, Noshirvan, A, Gregori, S, Roncarolo, MG, Nadeau, KC & Bacchetta, R 2018, 'Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired', Journal of Allergy and Clinical Immunology, vol. 141, no. 1, pp. 202-213.e8. https://doi.org/10.1016/j.jaci.2017.05.045
Pellerin, L ; Jenks, JA ; Chinthrajah, S ; Dominguez, T ; Block, W ; Zhou, X ; Noshirvan, A ; Gregori, S ; Roncarolo, MG ; Nadeau, KC ; Bacchetta, R. / Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired. In: Journal of Allergy and Clinical Immunology. 2018 ; Vol. 141, No. 1. pp. 202-213.e8.
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abstract = "Background: Peanut allergy (PA) is a life-threatening condition that lacks regulator-approved treatment. Regulatory T type 1 (T R 1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro by using tolerogenic dendritic cells. Whether oral immunotherapy (OIT) leads to antigen-specific T R 1 cell induction has not been established. Objectives: We sought to determine whether peanut-specific T R 1 cells can be generated in vitro from peripheral blood of patients with PA at baseline or during OIT and whether they are functional compared with peanut-specific T R 1 cells induced from healthy control (HC) subjects. Methods: Tolerogenic dendritic cells were differentiated in the presence of IL-10 from PBMCs of patients with PA and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h 1 and 2, and used as antigen-presenting cells for autologous CD4 + T cells (CD4 + T cells coincubated with tolerogenic dendritic cells pulsed with the main peanut allergens [pea-T10 cells]). Pea-T10 cells were characterized by the presence of CD49b + lymphocyte-activation gene 3 (LAG3) + T R 1 cells, antigen-specific proliferative responses, and cytokine production. Results: CD49b + LAG3 + T R 1 cells were induced in pea-T10 cells at comparable percentages from HC subjects and patients with PA. Despite their antigen specificity, pea-T10 cells of patients with PA with or without OIT, as compared with those of HC subjects, were not anergic and had high T H 2 cytokine production upon peanut-specific restimulation. Conclusions: Peanut-specific T R 1 cells can be induced from HC subjects and patients with PA, but those from patients with PA are functionally defective independent of OIT. The unfavorable T R 1/T H 2 ratio is discussed as a possible cause of PA T R 1 cell impairment. {\circledC} 2017 American Academy of Allergy, Asthma & Immunology.",
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T1 - Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired

AU - Pellerin, L

AU - Jenks, JA

AU - Chinthrajah, S

AU - Dominguez, T

AU - Block, W

AU - Zhou, X

AU - Noshirvan, A

AU - Gregori, S

AU - Roncarolo, MG

AU - Nadeau, KC

AU - Bacchetta, R

PY - 2018

Y1 - 2018

N2 - Background: Peanut allergy (PA) is a life-threatening condition that lacks regulator-approved treatment. Regulatory T type 1 (T R 1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro by using tolerogenic dendritic cells. Whether oral immunotherapy (OIT) leads to antigen-specific T R 1 cell induction has not been established. Objectives: We sought to determine whether peanut-specific T R 1 cells can be generated in vitro from peripheral blood of patients with PA at baseline or during OIT and whether they are functional compared with peanut-specific T R 1 cells induced from healthy control (HC) subjects. Methods: Tolerogenic dendritic cells were differentiated in the presence of IL-10 from PBMCs of patients with PA and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h 1 and 2, and used as antigen-presenting cells for autologous CD4 + T cells (CD4 + T cells coincubated with tolerogenic dendritic cells pulsed with the main peanut allergens [pea-T10 cells]). Pea-T10 cells were characterized by the presence of CD49b + lymphocyte-activation gene 3 (LAG3) + T R 1 cells, antigen-specific proliferative responses, and cytokine production. Results: CD49b + LAG3 + T R 1 cells were induced in pea-T10 cells at comparable percentages from HC subjects and patients with PA. Despite their antigen specificity, pea-T10 cells of patients with PA with or without OIT, as compared with those of HC subjects, were not anergic and had high T H 2 cytokine production upon peanut-specific restimulation. Conclusions: Peanut-specific T R 1 cells can be induced from HC subjects and patients with PA, but those from patients with PA are functionally defective independent of OIT. The unfavorable T R 1/T H 2 ratio is discussed as a possible cause of PA T R 1 cell impairment. © 2017 American Academy of Allergy, Asthma & Immunology.

AB - Background: Peanut allergy (PA) is a life-threatening condition that lacks regulator-approved treatment. Regulatory T type 1 (T R 1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro by using tolerogenic dendritic cells. Whether oral immunotherapy (OIT) leads to antigen-specific T R 1 cell induction has not been established. Objectives: We sought to determine whether peanut-specific T R 1 cells can be generated in vitro from peripheral blood of patients with PA at baseline or during OIT and whether they are functional compared with peanut-specific T R 1 cells induced from healthy control (HC) subjects. Methods: Tolerogenic dendritic cells were differentiated in the presence of IL-10 from PBMCs of patients with PA and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h 1 and 2, and used as antigen-presenting cells for autologous CD4 + T cells (CD4 + T cells coincubated with tolerogenic dendritic cells pulsed with the main peanut allergens [pea-T10 cells]). Pea-T10 cells were characterized by the presence of CD49b + lymphocyte-activation gene 3 (LAG3) + T R 1 cells, antigen-specific proliferative responses, and cytokine production. Results: CD49b + LAG3 + T R 1 cells were induced in pea-T10 cells at comparable percentages from HC subjects and patients with PA. Despite their antigen specificity, pea-T10 cells of patients with PA with or without OIT, as compared with those of HC subjects, were not anergic and had high T H 2 cytokine production upon peanut-specific restimulation. Conclusions: Peanut-specific T R 1 cells can be induced from HC subjects and patients with PA, but those from patients with PA are functionally defective independent of OIT. The unfavorable T R 1/T H 2 ratio is discussed as a possible cause of PA T R 1 cell impairment. © 2017 American Academy of Allergy, Asthma & Immunology.

U2 - 10.1016/j.jaci.2017.05.045

DO - 10.1016/j.jaci.2017.05.045

M3 - Article

VL - 141

SP - 202-213.e8

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

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ER -