Chopra, Martin and Biehl, Marlene and Steinfatt, Tim and Brandl, Andreas and Kums, Juliane and Amich, Jorge and Vaeth, Martin and Kuen, Janina and Holtappels, Rafaela and Podlech, Juergen and Mottok, Anja and Kraus, Sabrina and Jordan-Garrote, Ana-Laura and Baeuerlein, Carina A. and Brede, Christian and Ribechini, Eliana and Fick, Andrea and Seher, Axel and Polz, Johannes and Ottmueller, Katja J. and Baker, Jeanette and Nishikii, Hidekazu and Ritz, Miriam and Mattenheimer, Katharina and Schwinn, Stefanie and Winter, Thorsten and Schaefer, Viktoria and Krappmann, Sven and Einsele, Hermann and Mueller, Thomas D. and Reddehase, Matthias J. and Lutz, Manfred B. and Maennel, Daniela N. and Berberich-Siebelt, Friederike and Wajant, Harald and Beilhack, Andreas (2016) Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion. JOURNAL OF EXPERIMENTAL MEDICINE, 213 (9). pp. 1881-1900. ISSN 0022-1007, 1540-9538
Full text not available from this repository. (Request a copy)Abstract
Donor CD4(+) Foxp(3+) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; BONE-MARROW-TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; REGULATORY-CELLS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; FACTOR RECEPTOR; ALPHA THERAPY; EXPRESSION; SUPPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Apr 2019 09:21 |
| Last Modified: | 05 Apr 2019 09:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3466 |
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