Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction
Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction
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DOI：
10.1038/ni879
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发表时间：
2003-02-01
影响因子：
30.5
通讯作者：
Matsushima, K
中科院分区：
文献类型：
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作者：
Murai, M;Yoneyama, H;Matsushima, K
急性移植物抗宿主病（a-GVHD）主要由表达抗宿主特异性的免疫活性细胞毒性T细胞（CTL）引发。然而，这些前体CTL最初被刺激的宿主淋巴区室仍不清楚。在这里，我们表明，肠道派尔集合淋巴结（PP）激活抗宿主CTL反应，在一个很好的特点是小鼠急性移植物抗宿主反应（a-GVHR）模型，涉及转移到F1杂交受体的亲本淋巴细胞。当通过破坏编码趋化因子受体CCR 5的基因或通过阻断整合素α（4）β（7）-MAdCAM- 1（粘膜血管地址素）相互作用来中断供体T细胞向PP的募集时，a-GVHR就会被阻止。在两种疾病诱导模型中，PP缺陷的小鼠未能发生a-GVHD。因此，阻断PP中CTL的产生可能为规避a-GVHD提供新的策略。
Acute graft-versus-host disease (a-GVHD) is initiated primarily by immunologically competent cytotoxic T cells (CTLs) that express anti-host specificities. However, the host lymphoid compartment in which these precursor CTLs are initially stimulated remains unclear. Here we show that gut Peyer's patches (PPs) are required to activate anti-host CTL responses in a well characterized murine acute graft-versus-host reaction (a-GVHR) model, involving transfer of parent lymphocytes into F1 hybrid recipients. The a-GVHR was prevented when recruitment of donor T cells into PP was interrupted either by disrupting the gene encoding chemokine receptor CCR5 or by blocking integrin alpha(4)beta(7)-MAdCAM- 1 (mucosal vascular addressin) interactions. Mice deficient for PPs failed to develop a-GVHD in two models of disease induction. Thus, blockade of CTL generation in PPs might offer new strategies for circumventing a-GVHD.