Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation.
Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation.
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DOI：
10.1084/jem.20101709
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发表时间：
2011-05-09
期刊：
影响因子：
--
通讯作者：
Merad M
中科院分区：
文献类型：
--
作者：
Hashimoto D;Chow A;Greter M;Saenger Y;Kwan WH;Leboeuf M;Ginhoux F;Ochando JC;Kunisaki Y;van Rooijen N;Liu C;Teshima T;Heeger PS;Stanley ER;Frenette PS;Merad M
宿主巨噬细胞部分通过吞噬供体T细胞并抑制其增殖来防止移植物抗宿主病。急性移植物抗宿主病（GVHD）是由供体异基因T细胞攻击宿主组织引起的，是异基因造血细胞移植（allo-HCT）最严重的限制。宿主抗原呈递细胞被认为控制同种异体反应性T细胞的引发和allo-HCT后急性GVHD的诱导。然而，尽管宿主DC在GVHD中的作用已经确定，但宿主巨噬细胞对GVHD的贡献尚未得到明确解决。我们发现，与DC相反，受体小鼠中宿主巨噬细胞池的减少增加了供体T细胞的扩增，加重了allo-HCT后GVHD的死亡率。我们还表明，宿主巨噬细胞，坚持后allo-HCT吞噬供体同种异体T细胞，并抑制其增殖。相反，移植前给予细胞因子CSF-1可扩增宿主巨噬细胞库，减少供体T细胞扩增，并改善allo-HCT后GVHD发病率和死亡率。本研究确立了宿主巨噬细胞在抑制GVHD中的意想不到的关键作用，并将CSF-1鉴定为临床上限制allo-HCT后急性GVHD的潜在预防性治疗。
Host macrophages protect against graft-versus-host disease in part by engulfing donor T cells and inhibiting their proliferation. 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.
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DOI：
10.1084/jem.194.4.541
发表时间：
2001-08-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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发表时间：
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期刊：
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影响因子：
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