Experimentally induced accumulation of Foxp3+ T cells in upper airway allergy

• Published in: Clinical and experimental allergy Vol. 41; no. 7; pp. 954 - 962
• Main Authors: Skrindo, I., Scheel, C., Johansen, F.-E., Jahnsen, F. L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-07-2011; Blackwell; Wiley Subscription Services, Inc
• Subjects: Adult; Allergens; Allergens - immunology; Allergic rhinitis; Allergies; allergy; Animals; Biological and medical sciences; Biopsy; Bone; Cats; CD25 antigen; CD3 antigen; CD4 antigen; Cell activation; Cell proliferation; CTLA-4 protein; Dogs; Effector cells; Eosinophils - immunology; Forkhead Transcription Factors - metabolism; Foxp3; Foxp3 protein; Fundamental and applied biological sciences. Psychology; Fundamental immunology; human; Humans; Hypersensitivity; Immunofluorescence; Inflammation; Leukocytes (eosinophilic); Lymphocytes; Lymphocytes T; Male; Medical sciences; Mucosa; Nasal Mucosa - cytology; Nasal Mucosa - immunology; Nasal Provocation Tests; Non tumoral diseases; Nose; Otorhinolaryngology. Stomatology; Peripheral blood; Pollen; Pollen - immunology; regulatory T cells; Respiratory tract; Respiratory tract diseases; Rhinitis, Allergic, Seasonal - immunology; Rhinitis, Allergic, Seasonal - metabolism; Rhinitis, Allergic, Seasonal - physiopathology; Skin Tests; T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Therapeutic applications; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Young Adult; Human; Immunopathology; Allergy; Nose disease; Rhinitis; Upper respiratory tract; T cells; regulatory T cells; Immunology; T-Lymphocyte; ENT disease; allergic rhinitis; Foxp3; Regulatory cell; Transcription factor FOXP3
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2011.03710.x

Summary
Background
It has been suggested that Foxp3+ regulatory T (Treg) cells inhibit allergic inflammation in humans by suppressing the activation of allergen‐specific effector T cells. Whether this occurs at the site of allergen exposure has not been determined.
Objective
To determine the occurrence of Foxp3+ Treg cells in the nasal mucosa of allergic rhinitis (AR) patients and non‐allergic controls after a nasal allergen challenge.
Methods
Pollen‐allergic patients (n=18) and non‐allergic volunteers (n=7) were challenged locally with pollen extract or placebo for 7 days outside the pollen season. Mucosal biopsies were obtained from the inferior turbinate on days 0, 1 and 7 and subjected to multi‐colour immunofluorescence and blood was drawn for eosinophil counts on days 0, 2, 5 and 7.
Results
Only AR patients receiving pollen extract experienced typical allergic symptoms and demonstrated increased levels of eosinophils in peripheral blood and nasal mucosa. In allergic patients, a transient early increase (day 1) in CD3+ T cells was observed in the nasal mucosa, followed by a significant increase of Foxp3high T cells at day 7. No changes were found in the control group. The majority of Foxp3high cells co‐expressed CTLA‐4, CD25 and CD4, and a substantial fraction expressed the proliferation marker Ki67.
Conclusion and Clinical Relevance
Experimentally induced inflammation in AR patients leads to an early inflammatory response followed by accumulation of Foxp3high T cells in the nasal mucosa. Our findings are similar to that observed in allergic airways of experimental mice, which suggest that Treg cells are operative in allergic upper airway inflammation. It should be explored whether Treg cells accumulating in the nasal mucosa could be targets for therapeutic intervention.
Cite this as: I. Skrindo, C. Scheel, F.‐E. Johansen and F. L. Jahnsen, Clinical & Experimental Allergy, 2011 (41) 954–962.