Laurence Pellerin1, Jennifer Anne Jenks2, Sharon Chinthrajah2, Tina Dominguez2, Whitney Block2, Xiaoying Zhou2, Arram Noshirvan2, Silvia Gregori3, Maria Grazia Roncarolo4, Kari Christine Nadeau2, Rosa Bacchetta5. 1. Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, Calif; Division of Pulmonary and Critical Care at Stanford University, Department of Medicine, Stanford, Calif; Division of Stem Cell Transplantation and Regenerative Medicine at Stanford University, and Department of Pediatrics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, Calif. 2. Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, Calif; Division of Pulmonary and Critical Care at Stanford University, Department of Medicine, Stanford, Calif. 3. San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy. 4. Division of Stem Cell Transplantation and Regenerative Medicine at Stanford University, and Department of Pediatrics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, Calif. 5. Division of Stem Cell Transplantation and Regenerative Medicine at Stanford University, and Department of Pediatrics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, Calif. Electronic address: rosab@stanford.edu.
Abstract
BACKGROUND: Peanut allergy (PA) is a life-threatening condition that lacks regulator-approved treatment. Regulatory T type 1 (TR1) 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 TR1 cell induction has not been established. OBJECTIVES: We sought to determine whether peanut-specific TR1 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 TR1 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)+ TR1 cells, antigen-specific proliferative responses, and cytokine production. RESULTS: CD49b+LAG3+ TR1 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 TR1 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 TR1/TH2 ratio is discussed as a possible cause of PA TR1 cell impairment.
BACKGROUND: Peanut allergy (PA) is a life-threatening condition that lacks regulator-approved treatment. Regulatory T type 1 (TR1) 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 TR1 cell induction has not been established. OBJECTIVES: We sought to determine whether peanut-specific TR1 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 TR1 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)+ TR1 cells, antigen-specific proliferative responses, and cytokine production. RESULTS: CD49b+LAG3+ TR1 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 TR1 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 TR1/TH2 ratio is discussed as a possible cause of PA TR1 cell impairment.
Authors: Markus M Xie; Qiang Chen; Hong Liu; Kai Yang; Byunghee Koh; Hao Wu; Soheila J Maleki; Barry K Hurlburt; Joan Cook-Mills; Mark H Kaplan; Alexander L Dent Journal: J Clin Invest Date: 2020-07-01 Impact factor: 14.808
Authors: Sara Anvari; Levi B Watkin; Charles G Minard; Kimberly Schuster; Oluwatomi Hassan; Aikaterini Anagnostou; Jordan S Orange; David B Corry; Carla M Davis Journal: PLoS One Date: 2022-05-26 Impact factor: 3.752