Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation

Daigo Hashimoto, Andrew Chow, Melanie Greter, Yvonne Saenger, Wing Hong Kwan, Marylene Leboeuf, Florent Ginhoux, Jordi C. Ochando, Yuya Kunisaki, Nico van Rooijen, Chen Liu, Takanori Teshima, Peter S. Heeger, E. Richard Stanley, Paul S. Frenette, Miriam Merad

研究成果: ジャーナルへの寄稿学術誌査読

129 被引用数 (Scopus)

抄録

Acute graft-versus-host disease (GVHD) results from the attack of host tissues by donor allogeneic T cells and is the most serious limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Host antigen-presenting cells are thought to control the priming of alloreactive T cells and the induction of acute GVHD after allo-HCT. However, whereas the role of host DC in GVHD has been established, the contribution of host macrophages to GVHD has not been clearly addressed. We show that, in contrast to DC, reducing of the host macrophage pool in recipient mice increased donor T cell expansion and aggravated GVHD mortality after allo-HCT. We also show that host macrophages that persist after allo-HCT engulf donor allogeneic T cells and inhibit their proliferation. Conversely, administration of the cytokine CSF-1 before transplant expanded the host macrophage pool, reduced donor T cell expansion, and improved GVHD morbidity and mortality after allo-HCT. This study establishes the unexpected key role of host macrophages in inhibiting GVHD and identifies CSF-1 as a potential prophylactic therapy to limit acute GVHD after allo-HCT in the clinic.

本文言語英語
ページ(範囲)1069-1082
ページ数14
ジャーナルJournal of Experimental Medicine
208
5
DOI
出版ステータス出版済み - 5月 2011
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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