Grass pollen immunotherapy induces Foxp3-expressing CD4+CD25+ cells in the nasal mucosa
Received 27 June 2007; received in revised form 10 March 2008; accepted 18 March 2008. published online 23 April 2008.
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.
Department of Upper Respiratory Medicine, Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College and Royal Brompton Hospital London, London, United Kingdom
Reprint requests: Kayhan T. Nouri-Aria, PhD, Allergy and Clinical Immunology, National Heart and Lung Institute at Imperial College London, Sir Alexander Fleming Building, London SW7 2AZ, United Kingdom.
Funding for this project was from the Medical Research Council UK. K.T.N.-A. was supported by the Advanced Drug Discovery Initiative, a collaborative project between Imperial College Trust and GlaxoSmithKline. ALK-Abelló, Hørsholm, Denmark, supported the clinical trial of grass pollen subcutaneous immunotherapy.
Disclosure of potential conflict of interest: S. R. Durham has consulting arrangements with ALK-Abelló; has received research support from ALK-Abelló; is partially funded by the Immune Tolerance Network of the National Institutes of Health; and is on the speakers' bureau for ALK-Abelló, Allergy Therapeutics, and Stallergenes. The rest of the authors have declared that they have no conflict of interest.
ABSTRACT