Induction and maintenance of allergen-specific FOXP3+ Treg cells in human tonsils as potential first-line organs of oral tolerance - 03/02/12
, Beate Rückert a, Tuomas Jartti, MD b, Umut Can Kücüksezer, MD, PhD a, d, Tuomo Puhakka, MD c, e, Enrique Gomez, PhD a, Heinz B. Fahrner, MD f, Andreas Speiser, MD g, Andreas Jung, MD a, h, William W. Kwok, PhD i, Livije Kalogjera, MD j, Mübeccel Akdis, MD, PhD a, Cezmi A. Akdis, MD a, ⁎ 
Corresponding authors: Cezmi A. Akdis, MD, and Oscar Palomares, PhD, Swiss Institute of Allergy and Asthma Research (SIAF), Obere Str. 22, CH-7270, Davos Platz, Switzerland.Abstract |
Background |
Tonsils are strategically located in the gateway of both alimentary and respiratory tracts representing the first contact point of food and aeroallergens with the immune system. Tonsillectomy removes only the palatine tonsils and sometimes adenoids. Lingual tonsil is anatomically big and remains lifelong intact.
Objective |
The aim of this study was to demonstrate cellular and molecular mechanisms of oral tolerance induction to food and aeroallergens in human tonsils.
Methods |
Tonsil allergen-specific FOXP3+ regulatory T (Treg) cells, plasmacytoid dendritic cells (pDCs), and myeloid dendritic cells were characterized by flow cytometry and suppressive assays. Intracellular staining, [3H]-thymidine incorporation, and carboxy-fluorescein succinimidyl ester dilution experiments were performed. Tonsil biopsies were analyzed by confocal microscopy.
Results |
CD4+FOXP3+ Treg cells and pDCs constitute important T- and dendritic cell–compartments in palatine and lingual tonsils. Tonsil pDCs have the ability to generate functional CD4+CD25+CD127−FOXP3+ Treg cells with suppressive property from naive T cells. CD4+FOXP3+ Treg cells proliferate and colocalize with pDCs in vivo in T-cell areas of lingual and palatine tonsils. Tonsil T cells did not proliferate to common food and aeroallergens. Depletion of FOXP3+ Treg cells enables the allergen-induced proliferation of tonsil T cells, indicating an active role of Treg cells in allergen-specific T-cell unresponsiveness. High numbers of major birch pollen allergen, Bet v 1–specific CD4+FOXP3+ Treg cells, are identified in human tonsils compared with peripheral blood. A positive correlation between the percentages of FOXP3+ Treg cells and pDCs is observed in tonsils from nonatopic individuals.
Conclusion |
Functional allergen-specific Treg cells are identified both in lingual and in palatine tonsils.
Le texte complet de cet article est disponible en PDF.Key words : Immune tolerance, tonsils, allergen-specific Treg cells, plasmacytoid dendritic cells, myeloid dendritic cells
Abbreviations used : CFSE, DCs, mDCs, PC5, pDCs, TDCs, TLR, TMCs, Treg
Plan
| The authors’ laboratories are supported by Swiss National Foundation grants 32-125249 and 320030-132899 and Christine Kühne-Center for Allergy Research and Education (CK-CARE). O.P. was supported by a postdoctoral fellowship from Ministerio de Educación y Ciencia and FECYT (Spain) and W.W.K by NIH contract HHSN272200700046C. |
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| This work was supported by the European Commission’s Seventh Framework Programme under grant agreement no. 261357. |
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| Disclosure of potential conflict of interest: M. Akdis has received research support from the Swiss National Foundation, European Commission FP7 (MeDALL), and Predicta. C. A. Akdis has received research support from Novartis, Stallergenes, the Swiss National Science Foundation, Global Allergy and Asthma European Network, and Christine Kühne-Center for Allergy Research and Education; is a Fellow and interest group member of the American Academy of Allergy, Asthma & Immunology; is Vice President of the European Academy of Allergy and Clinical Immunology; and was a committee member for GA2LEN. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 2
P. 510 - février 2012 Retour au numéro
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