Grass pollen immunotherapy induces Foxp3-expressing CD4CD25 cells in the nasal mucosa

• Published in: Journal of allergy and clinical immunology 2008-06, Vol.121 (6), p.1467-1472.e1
• Main Authors: Radulovic, Suzana, Jacobson, Mikila R, Durham, Stephen R, Nouri-Aria, Kayhan T
• Format: Article
• Language: English
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2008.03.013

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-10expressing 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.