title: Induction and maintenance of allergen-specific FOXP3+ Treg cells in human tonsils as potential first-line organs of oral tolerance.
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, [(3)H]-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.
  
  
  CONCLUSIONS
  Functional allergen-specific Treg cells are identified both in lingual and in palatine tonsils.
authors: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland. oscar.palomares@quim.ucm.es
authors: Oscar
authors: O
authors: Palomares
authors: Beate
authors: B
authors: Rückert
authors: Tuomas
authors: T
authors: Jartti
authors: Umut Can
authors: UC
authors: Kücüksezer
authors: Tuomo
authors: T
authors: Puhakka
authors: Enrique
authors: E
authors: Gomez
authors: Heinz B
authors: HB
authors: Fahrner
authors: Andreas
authors: A
authors: Speiser
authors: Andreas
authors: A
authors: Jung
authors: William W
authors: WW
authors: Kwok
authors: Livije
authors: L
authors: Kalogjera
authors: Mübeccel
authors: M
authors: Akdis
authors: Cezmi A
authors: CA
authors: Akdis
mesh_terms: D000485:Allergens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007377:Interleukin-3 / Q000276:immunology; D014066:Palatine Tonsil / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D000485:Allergens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007377:Interleukin-3; D051193:Toll-Like Receptors