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Antigen in the Absence of DAMPs Promotes Immune Tolerance: The Role of Dendritic Cells and Regulatory T Cells

  • Walter Gottlieb Land
Chapter

Abstract

In this chapter, the emerging concept is discussed holding that the induction of immune tolerance is preferentially promoted by tolerogenic dendritic cells and regulatory T cells in situations where DAMPs are not present. In the first subchapter, the phenomenon of central T cell tolerance induced in the thymus is examined more carefully. The elimination of potentially dangerous self-reacting thymocytes is especially described by highlighting the mechanisms of clonal deletion/negative selection and clonal diversion that is mediated by thymic tolerogenic dendritic cells. These thymic DCs are involved in the creation of central tolerance via selection of thymic regulatory T cells.

Two subsequent subchapters are dedicated to the phenomenon of peripheral T cell tolerance which is induced by intrinsic mechanisms including processes of dendritic cell-mediated induction of T cell anergy and peripheral T cell deletion, as well as extrinsic mechanisms that refer to peripheral tolerogenic dendritic cell-mediated regulation of autoreactive T cells, mainly via generation of peripherally derived antigen-specific regulatory Foxp3+ T cells. This subset of T cells can suppress those lymphocytes reactive against (1) self antigens which have escaped central tolerance mechanisms in the thymus as well as (2) vital “life-protective” nonself antigens (e.g., dietary or commensal antigens) which do not exist in the thymus. Finally, particular attention is drawn to means and methods suitable to induce in vivo and/or in vitro human regulatory T cells. These efforts have led to some clinical trials to test the safety and efficacy of these immunosuppression-mediating cells in transplant patients or patients suffering from immunological disorders such as autoimmune diseases.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of StrasbourgMolecular ImmunoRheumatology, Laboratory of Excellence TransplantexStrasbourgFrance

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