Peanut-specific Tr1 cells induced in vitro from allergic individuals are functionally impaired

Publication date: Available online 6 July 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Laurence Pellerin, Jennifer Anne Jenks, Sharon Chinthrajah, Tina Dominguez, Whitney Block, Xiaoying Zhou, Arram Noshirvan, Silvia Gregori, Maria Grazia Roncarolo, Kari Christine Nadeau, Rosa Bacchetta
BackgroundPeanut allergy is a life threatening condition which lacks regulatory-approved treatment. T regulatory type 1 (Tr1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro using tolerogenic dendritic cells (DC-10). Whether or not oral immunotherapy (OIT) leads to antigen-specific Tr1 cell induction has not been established.ObjectivesTo determine whether peanut-specific Tr1 cells can be generated in vitro from peripheral blood of peanut allergic (PA) individuals at baseline or during OIT, and whether they are functional as compared to peanut-specific Tr1 cells induced from healthy controls (HC).MethodsDC-10 were differentiated in the presence of IL-10 from peripheral blood mononuclear cells of PA individuals and HC pulsed with the main peanut allergens Arachis hypogaea (Ara h) 1 and 2, and used as antigen presenting cells for autologous CD4⁺T cells (pea-T10). Pea-T10 cells were characterized by the presence of CD49b⁺LAG3⁺ Tr1 cells, antigen-specific proliferative responses, and cytokine production.ResultsCD49b⁺LAG3⁺ Tr1 cells were induced in pea-T10 cells at comparable percentages from HC and PA individuals. Despite their antigen specificity, pea-T10 cells of PA individuals with or without OIT, as compared to those of HC, were not anergic and had high Th2 cytokine production upon peanut-specific restimulation.ConclusionsPeanut-specific Tr1 cells can be induced from HC and PA individuals, but those from PA individuals are functionally defective independently of the OIT. The unfavorable Tr1/Th2 ratio is discussed as possible cause of PA-Tr1 cell impairment.

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