Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD
Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD
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DOI：
10.1111/j.1399-3046.2009.01279.x
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发表时间：
2010-06-01
影响因子：
1.3
通讯作者：
Okumura, Ko
中科院分区：
文献类型：
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作者：
Fujimura, Junya;Takeda, Kazuyoshi;Okumura, Ko
在T细胞上表达的共刺激分子对供体T细胞的激活起着关键的调节作用，并与同种异体骨髓移植后急性GVHD有关。我们研究了b7相关蛋白-1 （B7RP-1）与ICOS在急性GVHD小鼠模型中相互作用的作用，该模型接受T细胞缺失的BM细胞和脾细胞。阻断抗b7rp -1单抗可显著降低急性GVHD的致死率和症状。在抗b7rp -1单抗处理的受体小鼠中，观察到脾细胞对宿主异体抗原的明显低反应性。此外，与由WT CD8 T细胞和icos缺陷CD4 T细胞组成的T细胞受体相比，由icos缺陷CD8 T细胞和WT CD4 T细胞组成的T细胞受体的急性GVHD显著降低。这些结果表明，在小鼠急性GVHD模型中，B7RP-1/ICOS共刺激信号在异体抗原反应性供体T细胞（特别是CD8 T细胞）的激活中起作用，并且阻断B7RP-1/ICOS相互作用可能有助于选择性地操纵急性GVHD受体中的异体抗原反应性T细胞。
Co-stimulatory molecules expressed on T cells critically regulate donor T-cell activation and are implicated in acute GVHD after allogeneic BMT. We here investigated the role of interaction between B7-related protein-1 (B7RP-1) and ICOS in murine acute GVHD model that received T cell-depleted BM cells and splenocytes. Administration of blocking anti-B7RP-1 mAb significantly reduced the lethality and symptoms in acute GVHD. A significant hypo-responsiveness of splenocytes to host alloantigen was observed in the recipient mice treated with anti-B7RP-1 mAb. Moreover, acute GVHD was significantly reduced in the recipients of T cells composed of ICOS-deficient CD8 T cells and WT CD4 T cells compared with that in the recipients of T cells composed of WT CD8 T cells and ICOS-deficient CD4 T cells. These results suggested that B7RP-1/ICOS co-stimulatory signal plays a role in the activation of alloantigen-reactive donor T cells, particularly in CD8 T cells, in murine acute GVHD model, and that the blockade of B7RP-1/ICOS interaction may be useful for selectively manipulating allo-reactive T cells in the recipients with acute GVHD.