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

Martin Chopra, Marlene Biehl, Tim Steinfatt, Andreas Brandl, Juliane Kums, Jorge Amich Elias, Martin Vaeth, Janina Kuen, Rafaela Holtappels, Jürgen Podlech, Anja Mottok, Sabrina Kraus, Ana-Laura Jordán-Garrote, Carina A Bäuerlein, Christian Brede, Eliana Ribechini, Andrea Fick, Axel Seher, Johannes Polz, Katja J OttmüllerJeanette 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

Research output: Contribution to journalArticlepeer-review


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. 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.

Original languageEnglish
Pages (from-to)1881–1900
JournalJournal of Experimental Medicine
Issue number9
Publication statusPublished - 15 Aug 2016


Dive into the research topics of 'Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion'. Together they form a unique fingerprint.

Cite this