Double negative T cells mediate Lag3-dependent antigen-specific protection in allergic asthma

Dan Tian, Lu Yang, Song Wang, Yanbing Zhu, Wen Shi, Chunpan Zhang, Hua Jin, Yue Tian, Hufeng Xu, Guangyong Sun, Kai Liu, Zhongtao Zhang and Dong Zhang ()
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Dan Tian: Capital Medical University
Lu Yang: Capital Medical University
Song Wang: Capital Medical University
Yanbing Zhu: Capital Medical University
Wen Shi: Capital Medical University
Chunpan Zhang: Capital Medical University
Hua Jin: Capital Medical University
Yue Tian: Capital Medical University
Hufeng Xu: Capital Medical University
Guangyong Sun: Capital Medical University
Kai Liu: Capital Medical University
Zhongtao Zhang: Capital Medical University
Dong Zhang: Capital Medical University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12243-0

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