Grass pollen immunotherapy induces Foxp3-expressing CD4⁺CD25⁺ cells in the nasal mucosa

Background

Regulatory T (Treg) cells play an important role in controlling allergic inflammation. The transcription factor Foxp3 regulates the development and function of natural and adaptive CD4⁺CD25⁺ Treg cells.

Objectives

We sought to examine the effect of grass pollen injection immunotherapy on the numbers of Foxp3⁺CD4⁺ and Foxp3⁺CD25⁺ T cells in and out of season and their expression of IL-10 in the nasal mucosa of patients with hay fever.

Methods

Nasal biopsy specimens were obtained from untreated patients with hay fever, participants with grass pollen allergy who had received 2 years of immunotherapy, and healthy control subjects. Dual-immunofluorescence microscopy was used to enumerate and colocalize Foxp3 expression to CD4⁺ and CD25⁺ T cells in the nasal mucosa. Triple staining was performed to colocalize Foxp3⁺ cells to CD3⁺CD25⁺ and CD3⁺ IL-10–expressing cells.

Results

At peak season, numbers of Foxp3⁺CD25⁺ (P = .02) and Foxp3⁺CD4⁺ (P = .03) cells were significantly increased in the nasal mucosa of immunotherapy-treated patients compared with numbers before treatment. Foxp3⁺CD25⁺ (P = .03) and Foxp3⁺CD4⁺ (P = .04) cells were also greater in immunotherapy-treated patients out of season compared with those in untreated patients with hay fever. Within the immunotherapy-treated group, 20% of CD3⁺CD25⁺ cells expressed Foxp3, and 18% of Foxp3⁺CD3⁺ cells were IL-10 positive.

Conclusion

The presence of local Foxp3⁺CD25⁺CD3⁺ cells in the nasal mucosa, their increased numbers after immunotherapy, and their association with clinical efficacy and suppression of seasonal allergic inflammation support a putative role for Treg cells in the induction of allergen-specific tolerance in human subjects.

Key words: Foxp3, CD4⁺CD25⁺ Treg cells, IL-10, grass pollen immunotherapy, hay fever/allergic rhinitis

Abbreviations used: GP-IT, Grass pollen injection immunotherapy, IQR, Interquartile range, Treg, Regulatory T