Der p 1‐specific regulatory T‐cell response during house dust mite allergen immunotherapy

• Published in: Allergy (Copenhagen) 2019-05, Vol.74 (5), p.976-985
• Main Authors: Boonpiyathad, Tadech, Sokolowska, Milena, Morita, Hideaki, Rückert, Beate, Kast, Jeannette I., Wawrzyniak, Marcin, Sangasapaviliya, Atik, Pradubpongsa, Panitan, Fuengthong, Rattanaporn, Thantiworasit, Pattarawat, Sirivichayakul, Sunee, Kwok, William W., Ruxrungtham, Kiat, Akdis, Mübeccel, Akdis, Cezmi A.
• Format: Article
• Language: English
• Subjects: Allergens; allergen‐specific T cells; Allergic diseases; Allergic rhinitis; Allergies; Animals; Antigens, Dermatophagoides - immunology; antigen‐specific immunotherapy; Arthropod Proteins - immunology; Biomarkers; CD25 antigen; Cross-Sectional Studies; Cysteine Endopeptidases - immunology; Cytokines - metabolism; Der p 1 antigen; Desensitization, Immunologic - methods; Dust; Epitopes, T-Lymphocyte - immunology; Foxp3 protein; House dust; house dust mite allergy; Humans; Hypersensitivity - diagnosis; Hypersensitivity - immunology; Hypersensitivity - therapy; Immune Tolerance; Immunological tolerance; Immunotherapy; Leukocytes (mononuclear); Lymphocytes T; Major histocompatibility complex; Medical treatment; Mites; Nose; Patients; Peripheral blood mononuclear cells; Pyroglyphidae - immunology; Rhinitis; Symptom Assessment; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Transcription; Treg
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.13684

Background Allergen‐specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen‐specific regulatory T (Treg) cells. Methods We studied 25 allergic rhinitis patients undergoing subcutaneous house dust mite–specific immunotherapy. Peripheral blood mononuclear cells were studied before and after 10, 30 weeks, and 3 years of AIT. Der p 1‐specific T regulatory cell responses were investigated by characterization of Der p 1‐MHC class II tetramer–positive cells and correlated with nasal symptom score. Results Twelve of 25 AIT patients matched with their MHC class II expression to the Der p 1 peptide‐MHC class II tetramers. A significant increase in the numbers of Der p 1‐specific FOXP3+Helios+CD25+CD127− Treg cells after 30 weeks was observed, which slightly decreased after 3 years of AIT. In contrast, Der p 1‐specific immunoglobulin‐like transcript 3 (ILT3)+CD25+ Treg cells decreased substantially from baseline after 3 years of AIT. ILT3+ Treg cells displayed compromised suppressive function and low FOXP3 expression. In addition, Der p 1‐specific IL‐10 and IL‐22 responses have increased after 30 weeks, but only IL‐10+ Der p 1‐specific Treg cells remained present at high frequency after 3 years of AIT. Increased number of FOXP3+Helios+ and IL‐10+ and decreased ILT3+ Treg cell responses correlated with improved allergic symptoms. Conclusion The results indicate that AIT involves upregulation of the activated allergen‐specific Treg cells and downregulation of dysfunctional allergen‐specific Treg cell subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response. Allergen‐specific immunotherapy induces an increase in activated Treg cells, IL‐10‐producing Treg cells, IL‐22‐ producing Th cells, and reduces dysfunctional ILT3+ CD25+ Treg cells. Increased number of FOXP3+Helios+, IL‐10+ and decreased ILT3+ Treg cell responses correlated with improved allergic symptoms. Allergen‐specific immunotherapy improves clinical symptoms which relates to the correction of dysregulated T cell responses.