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Comparison of Immune Checkpoint Molecule Expression in Different Years of House Dust Mite Subcutaneous Immunotherapy
Zeynep Hızlı Demirkale1,2,3, Mehmet Fatih Alpkıray4, Ayşe Engin1
1Department of Immunology, İstanbul University, Aziz Sancar Institute of Experimental Medicine, İstanbul, Türkiye.
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.
