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.


OBJECTIVE
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.


CONCLUSIONS
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.
Radulovic
Suzana
S
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.
Jacobson
Mikila R
MR
Durham
Stephen R
SR
Nouri-Aria
Kayhan T
KT
D003888:Desensitization, Immunologic; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000096:biosynthesis; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology*; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D006109:Poaceae / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D006255:Rhinitis, Allergic, Seasonal / Q000517:prevention & control*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016753:Interleukin-10