Mechanisms of allergy and clinical immunologyTriggering of specific Toll-like receptors and proinflammatory cytokines breaks allergen-specific T-cell tolerance in human tonsils and peripheral blood
Section snippets
Study group
The study has been reviewed and approved by the ethics committees of the Cantons of Graubünden and Zürich and Satakunta Central Hospital, Pori, Finland. Heparinized peripheral blood samples from well-characterized nonallergic healthy and allergic donors were used in the study. Healthy buffy coats obtained from the Red Cross, Zurich, Switzerland, were used to optimize experimental conditions and general experiments with purified DC subsets. Noninflamed tonsils from patients undergoing
Characterization of the polyallergic atopic status in human palatine tonsils
To study mechanisms of breaking allergen-specific T-cell tolerance in human tonsils, we first analyzed whether these tissues reflect the classical features of allergic diseases at the T-cell level. Therefore we compared the mRNA expression levels of T-cell lineage–related cytokines and transcription factors in tonsillar tissues directly excised from a randomly selected population of 24 polyallergic atopic and 24 nonallergic control subjects. Experiments were performed without any stimulation to
Discussion
Our results show that tonsils are organs in which regulation of immune responses to allergens take place that show an essential difference in atopic patients, thus representing a very suitable in vivo model to assess mechanisms of breaking allergen-specific T-cell tolerance. We demonstrate how peripheral T-cell tolerance to major environmental allergens can be broken by triggering of TLR4 or TLR8 and by the proinflammatory cytokines IL-1β or IL-6 in human tonsils and peripheral blood. We also
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Supported by Swiss National Foundation grants 32-125249 and 320030-132899, the Christine Kühne-Center for Allergy Research and Education (CK-CARE), European 7th frame work projects MeDALL: Mechanisms of the Development of Allergy (no. 261357), and PREDICTA: Post-Infectious Immune Reprogramming and Its Association with Persistence and Chronicity of Respiratory Allergic Diseases (no. 260895). U.C.K. was funded by a European Respiratory Society (ERS) Long Term Research Fellowship (no. 288), and O.P. is a Ramon y Cajal Scholar funded by MINECO and the European Social Fund. U.C.K. is supported by University of Istanbul, Research Fund (no. 2826).
Disclosure of potential conflict of interest: T. Jartti has received research support from the Academy of Finland and Sigrid Juselius Foundation. C. A. Akdis has received research support from Novartis, PREDICTA, the Swiss National Science Foundation, MeDALL, the Global Allergy and Asthma European Network, and the Christine Kühne-Center for Allergy Research and Education; has provided consultation for Actellion, Aventis, Stallergenes, and Allergopharma; is president of the European Academy of Allergy and Clinical Immunology; is a fellow and interest group member for the American Academy of Allergy, Asthma & Immunology; is a former committee member of the Global Allergy and Asthma European Network; and is director of the Christine Kühne-Center for Allergy Research and Education. M. Akdis has received research support from the Swiss National Science Foundation, Predicta, and MeDALL. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.