Extra-thymically induced T regulatory cell subsets: The optimal target for antigen-specific immunotherapy

Johan Verhagen*, Anja Wegner, David C. Wraith

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

20 Citations (Scopus)


Antigen-specific immunotherapy aims to selectively restore tolerance to innocuous antigens in cases of autoimmune or allergic disease, without the need for general immune suppression. Although the principle of antigen-specific immunotherapy was discovered more than a century ago, its clinical application to date is limited, particularly in the control of autoimmunity. This has resulted mainly from a lack of in-depth understanding of the underlying mechanism. More recently, the differentiation of extra-thymically induced T regulatory (Treg) cell subsets has been shown to be instrumental in peripheral tolerance induction. Two main types of inducible Treg cells, interleukin-10-secreting or Foxp3<sup>+</sup>, have now been described, each with distinct characteristics and methods of therapeutic induction. It is crucial, therefore, to identify the suitability of either subset in the control of specific immune disorders. This review explores their natural function, the known mechanisms of therapeutic differentiation of either subset as well as their in vivo functionality and discusses new developments that may aid their use in antigen-specific immunotherapy, with a focus on autoimmune disease.

Original languageEnglish
Pages (from-to)171-181
Number of pages11
Issue number2
Early online date7 May 2015
Publication statusPublished - 1 Jun 2015

Bibliographical note

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  • Antigen specificity
  • Foxp3
  • Immunotherapy
  • Interleukin-10
  • Regulatory T cell


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