Allergen immunotherapy improves defective follicular regulatory T cells in patients with allergic rhinitis

Publication date: Available online 21 February 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Yin Yao, Zhi-Chao Wang, Nan Wang, Peng-Cheng Zhou, Cai-Ling Chen, Jia Song, Li Pan, Bo Liao, Xin-Hao Zhang, Yong-Shi Yang, Xiao-Yan Xu, Rong-Fei Zhu, Di Yu, Zheng Liu

Abstract

Background

The function of follicular regulatory T (Tfr) cells, especially in regulating IgE production in allergic diseases, is poorly understood.

Objective

To investigate the phenotype, function, and clinical relevance of Tfr cells in patients with allergic rhinitis (AR).

Methods

The phenotype and frequency of tonsillar and circulating Tfr cells were characterized by flow cytometry. The function of Tfr cells was examined in an assay by co-culturing with follicular helper T (Tfh) cells and B cells. The associations between the Tfr cells and the clinical features in AR patients before and after allergen immunotherapy (AIT) were analyzed.

Results

Tfr cells were detected in germinal centers of tonsils but, compared to non-AR subjects, the frequencies declined in AR patients allergic to house dust mites. Circulating Tfr cells in blood were phenotypically and numerically correlated with tonsillar Tfr cells and a reduction of circulating Tfr cells, but not total or CXCR5^- Treg cells, was noted in AR patients compared to healthy controls. Moreover, circulating Tfr cells in AR patients showed a specific defect in suppressing IgE production but were capable to suppress the production of other immunoglobulin types. We identified negative associations of circulating Tfr cell frequencies and function with antigen-specific IgE levels or disease severity in AR patients. After AIT, the frequencies and function of circulating Tfr cells were improved, which positively associated with disease remission.

Conclusion

The impairment of Tfr cells may contribute to aberrant IgE production in AR, and AIT improves defective Tfr cell function. Tfr cells may serve as a potential biomarker to monitor clinical response to AIT.

Graphical abstract

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