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Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion

Please always quote using this URN: urn:nbn:de:bvb:20-opus-187640
  • Donor CD4\(^+\)Foxp3\(^+\) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology. ExpandingDonor CD4\(^+\)Foxp3\(^+\) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology. Expanding radiation-resistant host T reg cells in recipient mice using a mouse TNFR2-selective agonist before allo-HCT significantly prolonged survival and reduced GvHD severity in a TNFR2-and T reg cell-dependent manner. The beneficial effects of transplanted T cells against leukemia cells and infectious pathogens remained unaffected. A corresponding human TNFR2-specific agonist expanded human T reg cells in vitro. These observations indicate the potential of our strategy to protect allo-HCT patients from acute GvHD by expanding T reg cells via selective TNFR2 activation in vivo.show moreshow less

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Metadaten
Author: Martin Chopra, Marlene Biehl, Tim Steinfatt, Andreas Brandl, Juliane Kums, Jorge Amich, Martin Vaeth, Janina Kuen, Rafaela Holtappels, Jürgen Podlech, Anja Mottok, Sabrina Kraus, Ana-Laura Jordán-Garotte, Carina A. Bäuerlein, Christian Brede, Eliana Ribechini, Andrea Fick, Axel Seher, Johannes Polz, Katja J. Ottmueller, Jeannette Baker, Hidekazu Nishikii, Miriam Ritz, Katharina Mattenheimer, Stefanie Schwinn, Thorsten Winter, Viktoria Schäfer, Sven Krappmann, Hermann Einsele, Thomas D. Müller, Matthias J. Reddehase, Manfred B. Lutz, Daniela N. Männel, Friederike Berberich-Siebelt, Harald Wajant, Andreas Beilhack
URN:urn:nbn:de:bvb:20-opus-187640
Document Type:Journal article
Faculties:Medizinische Fakultät / Pathologisches Institut
Medizinische Fakultät / Institut für Virologie und Immunbiologie
Medizinische Fakultät / Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Fakultät für Biologie / Julius-von-Sachs-Institut für Biowissenschaften
Language:English
Parent Title (English):Journal of Experimental Medicine
Year of Completion:2016
Volume:213
Issue:9
Pagenumber:1881-1900
Source:Journal of Experimental Medicine (2016) 213:9, 1881-1900. https://doi.org/10.1084/jem.20151563
DOI:https://doi.org/10.1084/jem.20151563
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Alpha therapy; Autoimmune diseases; Bone marrow transplantantation; Expression; Factor receptor; Graft-versus-leukemia; Regulatory-cells; Rheumatoid arthritis; Suppression; Tumor-necrosis-factor
Release Date:2020/06/17
Licence (German):License LogoCC BY-NC-SA: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Weitergabe unter gleichen Bedingungen