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

Chopra M, Biehl M, Steinfatt T, Brandl A, Kums J, Amich J, Vaeth M, Kuen J, Holtappels R, Podlech J, Mottok A, Kraus S, Jordan-Garrote AL, Baeuerlein CA, Brede C, Ribechini E, Fick A, Seher A, Polz J, Ottmueller KJ, Baker J, Nishikii H, Ritz M, Mattenheimer K, Schwinn S, Winter T, Schaefer V, Krappmann S, Einsele H, Mueller TD, Reddehase MJ, Lutz MB, Maennel DN, Berberich-Siebelt F, Wajant H, Beilhack A (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Journal of Experimental Medicine Rockefeller University Press

Book Volume: 213

Pages Range: 1881-900

Journal Issue: 9

DOI: 10.1084/jem.20151563

Abstract

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.

Authors with CRIS profile

Sven Krappmann Professur für Klinische Mikrobiologie und Immunologie

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) Universität Regensburg DE Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Stanford University US United States (USA) (US)

How to cite

APA:

Chopra, M., Biehl, M., Steinfatt, T., Brandl, A., Kums, J., Amich, J.,... Beilhack, A. (2016). Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion. Journal of Experimental Medicine, 213(9), 1881-900. https://doi.org/10.1084/jem.20151563

MLA:

Chopra, Martin, et al. "Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion." Journal of Experimental Medicine 213.9 (2016): 1881-900.

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