Effect of Inflammation on Costimulation Blockade‐Resistant Allograft Rejection
Effect of Inflammation on Costimulation Blockade‐Resistant Allograft Rejection
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DOI：
10.1111/j.1600-6143.2005.00768.x
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发表时间：
2005-04
影响因子：
8.8
通讯作者：
K. Habiro;H. Shimmura;Sakiko Kobayashi;M. Kotani;Y. Ishida;K. Tanabe;H. Toma;R. Abe
中科院分区：
文献类型：
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作者：
K. Habiro;H. Shimmura;Sakiko Kobayashi;M. Kotani;Y. Ishida;K. Tanabe;H. Toma;R. Abe
此前，我们报道了同种异体皮肤移植物被 CD8+ T 细胞介导的 CD28 和 CD40 配体双缺陷小鼠快速排斥。这些结果表明，除了 CD28 和 CD40 介导的共刺激之外，一些元件还为供体特异性 CD8+ T 细胞的激活提供刺激信号。在本报告中，我们研究了移植排斥过程中与移植相关的炎症对 CD8+ T 细胞的共刺激独立启动的作用。 B6 RAG1 KO 小鼠被移植 BALB/c-skin，并在移植后当天或 50 天过继转移同基因 CD8+ T 细胞。当阻断 CD28 和 CD40 介导的共刺激无法防止新鲜移植的皮肤移植物的急性排斥反应时，它可以有效地延迟愈合良好的皮肤移植物的排斥反应。这些结果表明，与移植相关的因素在诱导共刺激阻断抗性同种异体移植排斥反应中具有重要作用。共刺激阻断未能阻止 NK 细胞的急性移植物浸润和移植物内 IL-12 和 IL-15 表达的增加。这些因素可能触发移植物浸润和 CD8+ T 细胞启动，从而诱导共刺激阻断抗性同种异体移植排斥。
Previously, we reported that allogeneic skin grafts were rapidly rejected by CD28 and CD40 ligand double deficient mice mediated by CD8+ T cells. These results indicated that some elements in addition to CD28‐ and CD40‐mediated costimulation provide stimulatory signals for the activation of donor‐specific CD8+ T cells. In this report, we investigated the role of inflammation associated with transplantation on costimulation‐independent priming of CD8+ T cell during graft rejection. B6 RAG1 KO mice were transplanted with BALB/c‐skin and adoptively transferred with syngeneic CD8+ T cells the same day or 50 days after transplantation. When blockade of CD28‐ and CD40‐mediated costimulation failed to prevent acute rejection of freshly transplanted skin grafts, it efficiently delayed rejection of well‐healed skin grafts. These results showed that factors associated with transplantation have essential roles in inducing costimulation blockade‐resistant allograft rejection. Costimulation blockade failed to prevent acute graft‐infiltration of NK cells and increasing expression of intragraft IL‐12 and IL‐15. These factors may trigger the graft‐infiltration and priming of CD8+ T cells to induce costimulation blockade‐resistant allograft rejection.