Restoration of IFN-γ-Producing MAIT Cell Correlates to Beneficial Allergen Immunotherapy in Allergic Rhinitis Patients

Abstract

Background

Mucosal-associated invariant T cells (MAIT) are emerging as important regulators at mucosal surfaces. While these cells have been linked to a Th1-biased immune response and support for B cells, their roles in allergic diseases characterised by type 2 inflammation remain elusive. The study seeks to characterise MAIT cells in house dust mite (HDM)-induced allergic rhinitis (AR) and subsequent allergen immunotherapy (AIT), aiming to elucidate their clinical significance in AR and potential to enhance AIT effectiveness.

Methods

MAIT cells were assessed in patients with AR and individuals undergoing AIT. The ratio and cytokine-producing capacity of these cells were analysed to explore their correlations with AR progression and their responsiveness to HDM extracts and MAIT cell-specific agonists.

Results

In AR patients, there was an increase in the ratios of circulating MAIT cells and tonsil follicular T helper-like MAIT cells, alongside a decrease in the IFN-γ-producing MAIT cells. AIT restored their IFN-γ producing capacity, which was further boosted by T cell receptor (TCR) activation using MAIT cell-specific agonist-loaded artificial antigen-presenting cells (aAPCs). Synergistic effects of aAPCs and HDM enhance MAIT cell activation and IFN-γ production while reducing HDM-induced IgE levels in PBMC cocultures. Moreover, higher ratios of MAIT cells and IFN-γ-producing MAIT cells correlated with decreased IgE and increased IgG4 and improved clinical outcomes during AIT.

Conclusions

These findings underscore the compromised IFN-γ-producing MAIT cells in AR and their restoration following AIT and TCR stimulation, highlighting the cell's therapeutic potential and predictive value for clinical outcomes in AR and AIT.