Comparison of Immune Checkpoint Molecule Expression in Different Years of House Dust Mite Subcutaneous Immunotherapy on CD4+ T and Treg Cells in Children with Allergic Rhinitis

Abstract

Background: Allergen‐specific immunotherapy, a unique inducer of tolerance, may result in T cell exhaution. Aims: To investigate how the duration of house dust mite (HDM) subcutaneous immunotherapy (SCIT) affects the expression of major immune checkpoint (ICP) molecules on the surface of CD4+ T-helper and regulatory T (Treg) cells. Study Design: Cross-sectional study. Methods: We enrolled 28 children with HDM-induced allergic rhinitis (AR) and six controls. The study participants were divided into six groups: one group each of patients in their first, second, and third years of HDM-SCIT; one group each comprising those in the first year following HDM-SCIT and those on pharmacotherapy; and the control group. The expression of ICPs on CD4+ T and Treg cells was determined using flow cytometry, and plasma levels of soluble ICPs were estimated by ELISA. Results: Our results revealed a significant increase in the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3) on CD4+ T cells during the second and third years of SCIT, respectively. Additionally, a strong correlation was observed between the expression of CTLA-4 and T cell immunoglobulin and mucin domain containing molecule-3 in CD4+ T cells. Furthermore, we observed a significant correlation between the expressions of programmed cell death protein-1, CTLA-4, T cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif domain, and LAG-3 on both CD4+ T and Treg cells. A robust correlation was observed between the plasma levels of soluble ICPs. Conclusion: HDM-SCIT induces CD4+ T cell exhaution, which may contribute to tolerance induction in children with AR.