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

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Damage-Associated Molecular Patterns in Human Diseases

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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    Walter Gottlieb Land

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Land, W.G. (2018). Antigen in the Absence of DAMPs Promotes Immune Tolerance: The Role of Dendritic Cells and Regulatory T Cells. In: Damage-Associated Molecular Patterns in Human Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-78655-1_33

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