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

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Allergen‐specific immunotherapy (<jats:styled-content style="fixed-case">AIT</jats:styled-content>) 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:styled-content style="fixed-case">AIT</jats:styled-content>. Der p 1‐specific T regulatory cell responses were investigated by characterization of Der p 1‐<jats:styled-content style="fixed-case">MHC</jats:styled-content> class <jats:styled-content style="fixed-case">II</jats:styled-content> tetramer–positive cells and correlated with nasal symptom score.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Twelve of 25 <jats:styled-content style="fixed-case">AIT</jats:styled-content> patients matched with their <jats:styled-content style="fixed-case">MHC</jats:styled-content> class <jats:styled-content style="fixed-case">II</jats:styled-content> expression to the Der p 1 peptide‐<jats:styled-content style="fixed-case">MHC</jats:styled-content> class <jats:styled-content style="fixed-case">II</jats:styled-content> tetramers. A significant increase in the numbers of Der p 1‐specific <jats:styled-content style="fixed-case">FOXP</jats:styled-content>3<jats:sup>+</jats:sup>Helios<jats:sup>+</jats:sup><jats:styled-content style="fixed-case">CD</jats:styled-content>25<jats:sup>+</jats:sup><jats:styled-content style="fixed-case">CD</jats:styled-content>127<jats:sup>−</jats:sup> Treg cells after 30 weeks was observed, which slightly decreased after 3 years of <jats:styled-content style="fixed-case">AIT</jats:styled-content>. In contrast, Der p 1‐specific immunoglobulin‐like transcript 3 (<jats:styled-content style="fixed-case">ILT</jats:styled-content>3)<jats:sup>+</jats:sup><jats:styled-content style="fixed-case">CD</jats:styled-content>25<jats:sup>+</jats:sup> Treg cells decreased substantially from baseline after 3 years of <jats:styled-content style="fixed-case">AIT</jats:styled-content>. <jats:styled-content style="fixed-case">ILT</jats:styled-content>3<jats:sup>+</jats:sup> Treg cells displayed compromised suppressive function and low <jats:styled-content style="fixed-case">FOXP</jats:styled-content>3 expression. In addition, Der p 1‐specific <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐22 responses have increased after 30 weeks, but only <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10<jats:sup>+</jats:sup> Der p 1‐specific Treg cells remained present at high frequency after 3 years of <jats:styled-content style="fixed-case">AIT</jats:styled-content>. Increased number of <jats:styled-content style="fixed-case">FOXP</jats:styled-content>3<jats:sup>+</jats:sup>Helios<jats:sup>+</jats:sup> and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10<jats:sup>+</jats:sup> and decreased <jats:styled-content style="fixed-case">ILT</jats:styled-content>3<jats:sup>+</jats:sup> Treg cell responses correlated with improved allergic symptoms.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The results indicate that <jats:styled-content style="fixed-case">AIT</jats:styled-content> 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 <jats:styled-content style="fixed-case">AIT</jats:styled-content> is associated with improved clinical response.</jats:p></jats:sec>