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, after 10 weeks, 30 weeks and 3 years of AIT. Der p 1‐specific T regulatory cell responses was 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⁺, 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 cells subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response.

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