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Induction and maintenance of allergen-specific FOXP3(+) Treg cells in human tonsils as potential first-line organs of oral tolerance


Palomares, Oscar; Rückert, Beate; Jartti, Tuomas; Kücüksezer, Umut Can; Puhakka, Tuomo; Gomez, Enrique; Fahrner, Heinz B; Speiser, Andreas; Jung, Andreas; Kwok, William W; Kalogjera, Livije; Akdis, Mübeccel; Akdis, Cezmi A (2012). Induction and maintenance of allergen-specific FOXP3(+) Treg cells in human tonsils as potential first-line organs of oral tolerance. Journal of Allergy and Clinical Immunology, 129(2):510-520.e9.

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.
CONCLUSION:

Functional allergen-specific Treg cells are identified both in lingual and in palatine tonsils.

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.
CONCLUSION:

Functional allergen-specific Treg cells are identified both in lingual and in palatine tonsils.

Citations

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:February 2012
Deposited On:05 Apr 2012 13:52
Last Modified:05 Apr 2016 15:41
Publisher:Elsevier
ISSN:0091-6749
Publisher DOI:10.1016/j.jaci.2011.09.031
PubMed ID:22051696

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