期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 213, 期 9, 页码 1881-1900出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20151563
关键词
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资金
- Interdisziplinare Zentrum fur Klinische Forschung der Universitat Wurzburg [B-149, B-233]
- IFF-I program of the Johannes Gutenberg University, Mainz
- Deutsche Jose Carreras Leukamie-Stiftung e.V. [R/06/17, R/10/15]
- Deutsche Forschungsgemeinschaft [SFBTR 124, SFBTR 52, Wa 1025/18-1, KFO183, KFO 216, Ma 760/19-1]
- Else-Kroner-Fresenius-Stiftung [2010_Kolleg.52]
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.
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