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      Make immunological peace not war: Potential applications of tolerogenic dendritic cells

      editorial
      Author(s): ∗
      Publication date (Electronic):
      Journal: Biomedical Journal
      Publisher: Chang Gung University
      Keywords: Tolerogenic dendritic cells, Transplantation, Autoimmunity, Malaria diagnosis

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          Abstract

          In this issue of the Biomedical Journal, we explore the powerful immunosuppressive properties of tolerogenic dendritic cells and discuss their potential to bring about lifelong tolerance in transplantation and autoimmune disease. We also highlight an exciting new development in the field of malaria diagnosis that could facilitate early detection of the disease.

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          How tolerogenic dendritic cells induce regulatory T cells.

          Roberto Maldonado, Ulrich H. von Andrian (2010)
          Since their discovery by Steinman and Cohn in 1973, dendritic cells (DCs) have become increasingly recognized for their crucial role as regulators of innate and adaptive immunity. DCs are exquisitely adept at acquiring, processing, and presenting antigens to T cells. They also adjust the context (and hence the outcome) of antigen presentation in response to a plethora of environmental inputs that signal the occurrence of pathogens or tissue damage. Such signals generally boost DC maturation, which promotes their migration from peripheral tissues into and within secondary lymphoid organs and their capacity to induce and regulate effector T cell responses. Conversely, more recent observations indicate that DCs are also crucial to ensure immunological peace. Indeed, DCs constantly present innocuous self- and nonself-antigens in a fashion that promotes tolerance, at least in part, through the control of regulatory T cells (Tregs). Tregs are specialized T cells that exert their immunosuppressive function through a variety of mechanisms affecting both DCs and effector cells. Here, we review recent advances in our understanding of the relationship between tolerogenic DCs and Tregs. Copyright © 2010 Elsevier Inc. All rights reserved.
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            Consequences of Cell Death

            Birthe Sauter, Matthew L. Albert, Loise Francisco … (2000)
            Cell death by necrosis is typically associated with inflammation, in contrast to apoptosis. We have identified additional distinctions between the two types of death that occur at the level of dendritic cells (DCs) and which influence the induction of immunity. DCs must undergo changes termed maturation to act as potent antigen-presenting cells. Here, we investigated whether exposure to apoptotic or necrotic cells affected DC maturation. We found that immature DCs efficiently phagocytose a variety of apoptotic and necrotic tumor cells. However, only exposure to the latter induces maturation. The mature DCs express high levels of the DC-restricted markers CD83 and lysosome-associated membrane glycoprotein (DC-LAMP) and the costimulatory molecules CD40 and CD86. Furthermore, they develop into powerful stimulators of both CD4+ and CD8+ T cells. Cross-presentation of antigens to CD8+ T cells occurs after uptake of apoptotic cells. We demonstrate here that optimal cross-presentation of antigens from tumor cells requires two steps: phagocytosis of apoptotic cells by immature DCs, which provides antigenic peptides for major histocompatibility complex class I and class II presentation, and a maturation signal that is delivered by exposure to necrotic tumor cells, their supernatants, or standard maturation stimuli, e.g., monocyte-conditioned medium. Thus, DCs are able to distinguish two types of tumor cell death, with necrosis providing a control that is critical for the initiation of immunity.
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              CTLA-4 ligation blocks CD28-dependent T cell activation [published erratum appears in J Exp Med 1996 Jul 1;184(1):301]

              JA Bluestone, TL Walunas (1996)
              CTLA-4 is a CD28 homologue believed to be a negative regulator of T cell function. However, the mechanism of this downregulatory activity is not well understood. The present study was designed to examine the effect of CTLA-4 ligation on cytokine production, cell survival, and cell cycle progression. The results demonstrate that the primary effect of CTLA-4 ligation is not the induction of apoptosis. Instead, CTLA-4 signaling blocks IL-2 production, IL-2 receptor expression, and cell cycle progression of activated T cells. Moreover, the effect of CTLA-4 signaling was manifested after initial T cell activation. Inhibition of IL-2 receptor expression and cell cycle progression was more pronounced at late (72 h) time points after initial activation. The effects of anti-CTLA-4 mAbs were most apparent in the presence of optimal CD28- mediated costimulation consistent with the finding that CTLA-4 upregulation was CD28-dependent. Finally, the addition of exogenous IL- 2 to the cultures restored IL-2 receptor expression and T cell proliferation. These results suggest that CTLA-4 signaling does not regulate cell survival or responsiveness to IL-2, but does inhibit CD28- dependent IL-2 production.
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                Author and article information

                Contributors
                Emma Louise Walton
                Journal
                Journal ID (nlm-ta): Biomed J
                Journal ID (iso-abbrev): Biomed J
                Title: Biomedical Journal
                Publisher: Chang Gung University
                ISSN (Print): 2319-4170
                ISSN (Electronic): 2320-2890
                Publication date PMC-release: 08 May 2017
                Publication date (Print): April 2017
                Publication date (Electronic): 08 May 2017
                Volume: 40
                Issue: 2
                Pages: 77-79
                Affiliations
                [1]Staff Writer at the Biomedical Journal, 56 Dronningens Gate, 7012 Trondheim, Norway
                Author notes
                [∗ ]Corresponding author. ewalton86@ 123456gmail.com
                Article
                Publisher ID: S2319-4170(17)30137-3
                DOI: 10.1016/j.bj.2017.04.001
                PMC ID: 6138600
                PubMed ID: 28521904
                SO-VID: 834c4fe0-8370-4cd2-ba10-3a18f9c27b64
                Copyright © © 2017 Chang Gung University. Publishing services by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Subject: Highlight

                Keywords: tolerogenic dendritic cells,transplantation,autoimmunity,malaria diagnosis
                Data availability:
                Keywords: tolerogenic dendritic cells, transplantation, autoimmunity, malaria diagnosis

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