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Antigen-specific regulatory T-cell responses against aeroantigens and their role in allergy

Mucosal Immunology (2018) | Download Citation



The mucosal immune system of the respiratory tract is specialized to continuously monitor the external environment and to protect against invading pathogens, while maintaining tolerance to innocuous inhaled particles. Allergies result from a loss of tolerance against harmless antigens characterized by formation of allergen-specific Th2 cells and IgE. Tolerance is often described as a balance between harmful Th2 cells and various types of protective “regulatory” T cells. However, the identity of the protective T cells in healthy vs. allergic individuals or following successful allergen-specific therapy is controversially discussed. Recent technological progress enabling the identification of antigen-specific effector and regulatory T cells has significantly contributed to our understanding of tolerance. Here we discuss the experimental evidence for the various tolerance mechanisms described. We try to integrate the partially contradictory data into a new model proposing different mechanism of tolerance depending on the quality and quantity of the antigens as well as the way of antigen exposure. Understanding the basis of tolerance is essential for the rational design of novel and more efficient immunotherapies.

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This work was supported by grants from the Cystic Fibrosis Foundation (USA) (SCHEFF15G0), the German Federal Ministry of Education and Science (BMBF)—Project InfectControl 2020 (ART4Fun Fkz 03ZZ0813A and DIAT Fkz 03ZZ0827A), and the German Research Foundation (DFG, FKz Sche 670/2-1) to A.S. and by a grant from the Christiane Herzog Stiftung, Stuttgart, Germany and the Mukoviszidose e.V., Bonn, the German Cystic Fibrosis Association to P.B. We thank Margitta Worm and Guido Heine, Charité for critical reading of the manuscript.

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  1. Department of Cellular Immunology, Clinic for Rheumatology and Clinical Immunology, Charité—University Medicine Berlin, Berlin, Germany

    • Petra Bacher
  2. Institute of Immunology, University of Kiel/UKSH Campus Kiel, Kiel, Germany

    • Alexander Scheffold


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P.B. and A.S. contributed equally to the writing and editing of this review.

Competing interests

A.S. works as a consultant for Miltenyi Biotec who owns IP rights concerning the ARTE technology. P.B. declares no competing interests.

Corresponding author

Correspondence to Alexander Scheffold.

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