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

• Published in: Balkan medical journal Vol. 41; no. 5; pp. 387 - 395
• Main Authors: Hızlı Demirkale, Zeynep, Alpkıray, Mehmet Fatih, Engin, Ayşe, Sönmez, Aybars Deniz, Yücel, Esra, Tamay, Zeynep, Özdemir, Cevdet, Deniz, Günnur, Çetin Aktaş, Esin
• Format: Journal Article
• Language: English
• Published: Turkey Galenos Publishing House 06.09.2024
• Subjects: Adolescent; Animals; CD4-Positive T-Lymphocytes - immunology; Child; Cross-Sectional Studies; CTLA-4 Antigen - analysis; Desensitization, Immunologic - methods; Female; Humans; Male; Pyroglyphidae - immunology; Rhinitis, Allergic - blood; Rhinitis, Allergic - immunology; Rhinitis, Allergic - therapy; T-Lymphocytes, Regulatory - immunology
• ISSN: 2146-3123; 2146-3131; 2146-3131
• DOI: 10.4274/balkanmedj.galenos.2024.2024-6-19

Allergen-specific immunotherapy, a unique inducer of tolerance, may result in T cell exhaution. 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. Cross-sectional study. 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. 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. HDM-SCIT induces CD4 T cell exhaution, which may contribute to tolerance induction in children with AR.