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Anti-regulatory T cells

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Abstract

Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells, including indoleamine 2,3-dioxygenase (IDO), tryptophan 2,6-dioxygenase (TDO), programmed death-ligand 1 (PD-L1), and forkhead box P3 (Foxp3). These proteins are highly expressed in professional antigen-presenting cells under various physiological conditions, such as inflammation and stress. Therefore, self-reactive T cells that recognize such targets may be activated due to the strong activation signal given by their cognate targets. The current review describes the existing knowledge regarding these self-reactive anti-Tregs, providing examples of antigen-specific anti-Tregs and discussing their possible roles in immune homeostasis and their potential future clinical applications.

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Acknowledgments

This study was supported by the Danish Cancer Society, the Danish Council for Independent Research, Toyota Foundation, and Herlev Hospital. The funders did not have a role in the writing of the article or the decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Hematology, Center for Cancer Immune Therapy (CCIT), Copenhagen University Hospital, Herlev, 2730, Herlev, Denmark

    Mads Hald Andersen

  2. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

    Mads Hald Andersen

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Correspondence to Mads Hald Andersen.

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Conflict of interest

MHA is an author of different patent applications based on the use of CCL22, PD-L1, TDO, or IDO for vaccination. The rights of the patent applications have been transferred to Copenhagen University Hospital, Herlev, according to the Danish Law of Public Inventions at Public Research Institutions. MHA is a shareholder and board member of the company IO Biotech ApS that has the purpose of developing commercial IDO and PD-L1 vaccines for cancer treatment.

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This article is a contribution to the special issue on Cancer and Autoimmunity - Guest Editor: Mads Hald Andersen

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Andersen, M.H. Anti-regulatory T cells. Semin Immunopathol 39, 317–326 (2017). https://doi.org/10.1007/s00281-016-0593-x

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