Abstract
Abstract Allergic asthma is a chronic inflammatory disorder of the airways. Traditional therapeutic strategies have been unsatisfactory in controlling the underlying pathology. New approaches that specific overcome the detrimental effects of immune dysregulation in allergic asthma are required. We have identified a new differentiation pathway for CD4−CD8− (double negative, DN) T cells that exhibits the potent immunosuppressive function in vitro and in vivo. In this study, we adoptive transferred OVA323–339 primed DNT cells to a mouse model of ovalbumin (OVA)-induced allergic asthma intravenously. The adoptive transferred DN T cells mainly migrated to mediastinal lymph node and lung, exerted strong suppression on CD11b+ dendritic cells, T follicular helper (Tfh) cell proliferation and IL-21 secretion, which resulted in significantly ameliorated airway hyperresponsiveness, lung inflammation and granulocyte accumulation, markedly reduced mucus formation and OVA-IgG/IgE production. To understand the antigen-specific mechanism of DN T cell, which is lack of CD4 molecule, we investigated the role of Lag3 in allergen recognition of DN T cell. We demonstrated that Lag3 deficiency impaired the generation of OVA-specific DN T cells. DN T cells acquired MHC-II of dendritic cells to obtain antigen specificity with the assistance of Lag3 molecule mainly through a trogocytosis process. The effectiveness of ex vivo generated OVA-specific DN T cell to alleviate airway inflammation support the concept and the feasibility of potentially utilizing this novel cell-based therapeutic approach clinically for the treatment of allergic asthma.
Published Version
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