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CD27 expression on allergen-specific T cells: A new surrogate for successful allergen-specific immunotherapy?

  • Stefanie Gilles
    Affiliations
    Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center, Munich, Germany
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  • Claudia Traidl-Hoffmann
    Correspondence
    Corresponding author: Claudia Traidl-Hoffmann, MD, Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Biedersteinerstr 29, 80802 München, Germany.
    Affiliations
    Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center, Munich, Germany

    Department of Dermatology, Technische Universität Munich, Munich, Germany
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      To date, allergen-specific immunotherapy (ASIT) is the only causal treatment for allergic diseases. The principle of ASIT is to administer gradually increasing doses of allergen, either as allergen extracts or as recombinant allergen. The aim is to reprogram the allergen-specific immune response from a TH2-driven IgE-dominated response toward a tolerant state. By inducing immune tolerance to an allergen, diseases such as allergic rhinitis might even be prevented in progressing toward a severe chronic disorder, such as asthma. Although the concept of specific immunotherapy is more than 100 years old,
      • Ring J.
      • Gutermuth J.
      100 years of hyposensitization: history of allergen-specific immunotherapy (ASIT).
      our knowledge about the underlying immunologic mechanisms is limited (for overview, see Fig 1
      • Wambre E.
      • Delong J.H.
      • James E.A.
      • Lafond R.E.
      • Robinson D.
      • Kwok W.W.
      Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy.
      • Akdis C.A.
      • Akdis M.
      Mechanisms of allergen-specific immunotherapy.
      ). Moreover, some patients are clinically unresponsive to ASIT, and the identification of solid predictors for successful ASIT remains an unmet clinical need.
      Figure thumbnail gr1
      Fig 1Changes in T-cell and antigen responses during ASIT. In susceptible subjects naturally exposed to an allergen, dendritic cell (DC)–derived signals lead to the differentiation of TH2 cells, which induce specific IgE production in B cells. During ASIT, increasing doses of allergen are administered. Through mechanisms that are incompletely understood to date, this licenses DCs to induce the differentiation of regulatory T (Treg) cells, which functionally inhibit the allergen-specific effector cells and promote the production of specific inhibiting IgG4 antibodies by B cells. Wambre et al
      • Wambre E.
      • Delong J.H.
      • James E.A.
      • Lafond R.E.
      • Robinson D.
      • Kwok W.W.
      Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy.
      now provide evidence that in patients who successfully completed ASIT, allergen-specific effector (TH2) cells are selectively deleted while allergen-specific TH1-like cells prevail.
      Modified with permission from Akdis and Akdis.
      • Akdis C.A.
      • Akdis M.
      Mechanisms of allergen-specific immunotherapy.

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