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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:141

Article

Pellerin, Laurence^1,2,3,4  Jenks, Jennifer Anne^1,2  Chinthrajah, Sharon^1,2  Dominguez, Tina^1,2  Block, Whitney^1,2  Zhou, Xiaoying^1,2  Noshirvan, Arram^1,2  Gregori, Silvia⁵  Roncarolo, Maria Grazia^3,4  Nadeau, Kari Christine^1,2  Bacchetta, Rosa^3,4 

[1] Stanford Univ, Sean N Parker Ctr Allergy & Asthma Res, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Med, Div Pulm & Crit Care, Stanford, CA 94305 USA

[3] Stanford Univ, Div Stem Cell Transplantat & Regenerat Med, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Pediat, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[5] Ist Sci San Raffaele, IRCCS, San Raffaele Telethon Inst Gene Therapy SR TIGET, Milan, Italy

关键词: Peanut allergy;    oral immunotherapy;    T(R)1 cells;    LAG3;    CD49b;    T(H)2 cells;    Ara h 1/2;   

DOI  :  10.1016/j.jaci.2017.05.045

来源: Elsevier

【 摘 要 】

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 TH2 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/TH2 ratio is discussed as a possible cause of PA T(R)1 cell impairment.

【 授权许可】

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