Inhibition of donor‐derived T cells trafficking into target organs by FTY720 during acute graft‐versus‐host disease in small bowel transplantation
Inhibition of donor‐derived T cells trafficking into target organs by FTY720 during acute graft‐versus‐host disease in small bowel transplantation
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DOI：
10.1111/j.1365-2249.2006.03175.x
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发表时间：
2006-10
影响因子：
4.6
通讯作者：
J. Song;Toshinori Ito;C. Matsuda;Gang Miao;Masahiro Tanemura;Toshirou Nishida;M. Nozawa;Hideo Matsuda;Yoshiki Sawa
中科院分区：
文献类型：
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作者：
J. Song;Toshinori Ito;C. Matsuda;Gang Miao;Masahiro Tanemura;Toshirou Nishida;M. Nozawa;Hideo Matsuda;Yoshiki Sawa
在小肠移植（SBTx）中，移植物抗宿主病（GVHD）是由识别宿主主要组织相容性复合体（MHC）同种异体抗原的供体来源T细胞介导的，代表了影响实验和临床情况下生命的重要免疫学事件。我们评估了一种新的1-磷酸鞘氨醇受体激动剂FTY 720通过改变靶器官中供体来源的T细胞的交通量来减少大鼠SBTx模型中GVHD的可能性。使用亲代（WF）-入-F1（WF × ACI）大鼠组合进行异位SBTx。将小鼠存活率、体重、组织病理学、供体来源的T细胞亚群和细胞因子产生与未处理的对照进行比较。当以0.5 mg/kg给药时，FTY 720抑制靶器官的致死性和组织病理学变化，这可能是由于供体来源的T细胞在肠移植物中的隔离。FTY 720通过促进供体T细胞归巢到供体而不是受体的次级淋巴组织中，引起靶器官中供体T细胞数量的显著减少。FTY 720显著降低靶器官中干扰素（IFN）-γ的产生。这些发现表明，FTY 720有效地减少了GVHD中活化的供体来源的T细胞的再循环和向靶器官的募集，并且还与下调IFN-γ产生相关。这些特性可能提供治疗SBTx中正在进行的GVHD的潜力。
In small bowel transplantation (SBTx), graft‐versus‐host disease (GVHD) is mediated by donor‐derived T cells recognizing host major histocompatibility complex (MHC) alloantigens, and represents an important immunological event influencing life in experimental and clinical situations. We evaluated the possibility that a new sphingosine 1‐phosphate receptor agonist, FTY720, could diminish GVHD in a rat SBTx model through traffic alteration of donor‐derived T cells in target organs. Heterotopic SBTx was performed using a parent (WF)‐into‐F1 (WF × ACI) rat combination. Recipient survival, body weight, histopathology, donor‐derived T cell subpopulation and cytokine production were compared with untreated controls. FTY720 inhibited lethality and histopathological changes in target organs when administered at 0·5 mg/kg, possibly due to sequestration of donor‐derived T cells in the intestinal graft. FTY720 caused a significant reduction in donor T cell numbers in target organs by promoting these cells to home into donor, but not recipient, secondary lymphoid tissues. FTY720 significantly decreased production of interferon (IFN)‐γ in target organs. These findings indicate that FTY720 effectively reduced recirculation of activated donor‐derived T cells and recruitment to target organs in GVHD, and was also associated with down‐regulated IFN‐γ production. These properties may offer the potential to treat ongoing GVHD in SBTx.