Abstract
Allergic asthma is an inflammatory disorder of the airway without satisfactory traditional therapies capable of controlling the underlying pathology. New approaches that can overcome the detrimental effects of immune dysregulation are thus desirable. Here we adoptively transfer ovalbumin (OVA) peptide-primed CD4−CD8− double negative T (DNT) cells intravenously into a mouse model of OVA-induced allergic asthma to find that OVA-induced airway hyperresponsiveness, lung inflammation, mucus production and OVA-specific IgG/IgE production are significantly suppressed. The immunosuppressive function of the OVA-specific DNT cells is dependent on the inhibition of CD11b+ dendritic cell function, T follicular helper cell proliferation, and IL-21 production. Mechanistically, Lag3 contributes to MHC-II antigen recognition and trogocytosis, thereby modulating the antigen-specific immune regulation by DNT cells. The effectiveness of ex vivo-generated allergen-specific DNT cells in alleviating airway inflammation thus supports the potential utilization of DNT cell-based therapy for the treatment of allergic asthma.
Highlights
Allergic asthma is an inflammatory disorder of the airway without satisfactory traditional therapies capable of controlling the underlying pathology
These results demonstrated that double negative T (DNT) cells could restrict airway inflammation and ameliorate OVA-induced allergic asthma
The adoptively transferred OVA-primed DNT cells mainly accumulated in the lungs, BALF and spleen to significantly inhibit OVA-induced airway inflammation and suppress mucus hypersecretion, bronchial hyperreactivity and the infiltration of eosinophils and lymphocytes
Summary
Allergic asthma is an inflammatory disorder of the airway without satisfactory traditional therapies capable of controlling the underlying pathology. We adoptively transfer ovalbumin (OVA) peptide-primed CD4−CD8− double negative T (DNT) cells intravenously into a mouse model of OVA-induced allergic asthma to find that OVA-induced airway hyperresponsiveness, lung inflammation, mucus production and OVA-specific IgG/IgE production are significantly suppressed. The effectiveness of ex vivo-generated allergen-specific DNT cells in alleviating airway inflammation supports the potential utilization of DNT cell-based therapy for the treatment of allergic asthma. Allergic asthma is characterized by hyperresponsiveness, mucus production, inflammatory cell accumulation, and allergen-specific IgE secretion. We demonstrate that the adoptive transfer of DNT cells ameliorates ovalbumin (OVA)-induced airway hyperresponsiveness, lung inflammation, mucus production, inflammatory cell accumulation, and OVA-specific IgG/IgE production while preserving allergen specificity. We provide evidence that lymphocyte-activation gene 3 (Lag3) is a key molecule that contributes to MHC-II antigen recognition and trogocytosis and affects the antigen-specific immune regulation of DNT cells
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