The role of the B7 costimulatory pathway in experimental cold ischemia/reperfusion injury.
The role of the B7 costimulatory pathway in experimental cold ischemia/reperfusion injury.
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B7 共刺激通路在实验性冷缺血/再灌注损伤中的作用。
DOI：
10.1172/jci119632
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Tilney,NL
中科院分区：
文献类型：
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作者：
Takada,M;Chandraker,A;Nadeau,KC;Sayegh,MH;Tilney,NL
与器官获取和储存相关的缺血/再灌注损伤影响慢性移植物功能障碍的发展，这是实体器官移植中的主要临床问题。单核细胞（T细胞和单核细胞/巨噬细胞）在这种类型的损伤中的潜在作用尚不清楚。将近交系雄性刘易斯大鼠单肾切除，并将左肾用10 ml冰冻的威斯康星州大学溶液原位灌注。免疫组化研究表明，与MHC II类抗原表达上调的缺血器官的单核细胞浸润。逆转录-PCR表明，T细胞相关的细胞因子和单核细胞/巨噬细胞活化标志物/产物在缺血损伤后早期上调。B7在24 h内开始表达，3 d达高峰。血浆肌酐水平一过性升高，5 d时肾功能完全恢复。动物在8-12周后开始出现进行性蛋白尿，表明早期缺血/再灌注损伤的长期功能后果。用CTLA 4 Ig阻断T细胞CD 28-B7共刺激可显著抑制T细胞和巨噬细胞的原位浸润和活化。给药动物未表现出一过性肾功能不全，也未随时间推移出现蛋白尿。这是第一次证明，在同种异体抗原的情况下阻断T细胞共刺激激活可以预防缺血/再灌注损伤的早期和晚期后果。
Ischemia/reperfusion injury associated with organ retrieval and storage influences the development of chronic graft dysfunction, the major clinical problem in solid organ transplantation. The potential role of mononuclear cells (T cells and monocyte/macrophages) in this type of injury is unknown. Inbred male Lewis rats were uninephrectomized and the left kidney perfused in situ with 10 ml of iced University of Wisconsin solution. Immunohistological studies showed mononuclear cell infiltration of the ischemic organs associated with the upregulation of MHC class II antigen expression. Reverse transcriptase-PCR indicated that T cell associated cytokines and monocyte/macrophage activation markers/products are upregulated early after the ischemic insult. B7 expression occurred within 24 h and peaked at 3 d. Plasma creatinine levels rose transiently with complete recovery of renal function by 5 d. Animals began to develop progressive proteinuria after 8-12 wk, indicative of the long-term functional consequences of early ischemia/reperfusion injury. Blockade of T cell CD28-B7 costimulation with CTLA4Ig resulted in significant inhibition of T cell and macrophage infiltration and activation in situ. Treated animals did not exhibit transient renal dysfunction, nor developed proteinuria over time. This is the first demonstration that blocking T cell costimulatory activation in the absence of alloantigen can prevent the early and late consequences of ischemia/reperfusion injury.