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

Abstract

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 tetramerpositive 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. K E Y W O R D Sallergen-specific T cells, antigen-specific immunotherapy, house dust mite allergy, Treg Abbreviations: AIT, antigen-specific immunotherapy; AR, allergic rhinitis; HDM, house dust mite; ILT3, immunoglobulin-like transcript 3; Treg, T regulatory.

Allergen‐specific immunotherapy boosts allergen‐specific IgD production in house dust mite‐sensitized asthmatic patients

“…4 Whereas AIT is an effective treatment in the patients with house dust mites (HDM) allergy, the role of HDM allergen-specific IgD remains to be fully evaluated. 4,7 The major HDM allergens are represented by Der p/f 1, Der p/f 2, and Der p/f 23. 8 In this report, we have shown that Der p 2-specific IgD-producing B cells increased during the course of AIT that might be correlated to the successful development of HDM tolerance.…”

“…From a cohort study of 75 HDM allergic patients undergoing SCIT with HDM allergen extracts, we selected 6 treated asthmatic patients to investigate Der p 2-specific B cells. 4,7 The patient characteristics are shown in the Table S1. Peripheral blood mononuclear F I G U R E 2 Improved asthma control correlated with plasma Der p 2-specific IgD levels.…”

Recent developments and highlights in immune monitoring of allergen immunotherapy

“…113 Furthermore, allergen-specific Tregs have been shown to expand following AIT for HDM and grass pollen allergies thereby increasing the ratio of allergen-specific Tregs over effector T cells. 32,33,114,115 To facilitate translation towards routine measurements of T-cell biomarkers, immunophenotyping approaches have been developed that only use membrane markers and allow for direct ex vivo T-cell evaluation without in vitro cell culture. The CD4+CD25+CD127phenotype specifically distinguishes human Treg, 116,117 and these cells can be quantified in allergic patients 31 with increases following SLIT for grass pollen 11 and AIT in HDM-allergic individuals.…”

“…The CD4+CD25+CD127phenotype specifically distinguishes human Treg, 116,117 and these cells can be quantified in allergic patients 31 with increases following SLIT for grass pollen 11 and AIT in HDM-allergic individuals. 32 Furthermore, chemokine receptor expression patterns correlate strongly with Th cell function [118][119][120] and can be used to identify Th1 (CCR6-CXCR3+CCR4-), Th2 (CCR6-CXCR3-CCR4+) and Th17…”

“…30,31,42,121 With the use of MHC-peptide reagents to detect antigen specificity, 115 the sensitivity of these changes can be significantly enhanced to detect early effects of AIT. 32,113 As the application of MHC tetramers, especially for MHC class II, is limited by the diversity of alleles in the human population, there is a need for alternative markers for allergen-specific cells. In early immunophenotyping studies of allergen-specific cells, the CD27-CRTh2 + phenotype was shown to correlate well with the Th2-skewed (CCR4+) subset, 124 and CD4 T cells with this phenotype (CCR4+CD27-CRTh2+) were specifically reduced in patients with birch pollen-related apple allergy following SLIT with recombinant Mal d 1.…”