Liver grafts from CD39-overexpressing rodents are protected from ischemia reperfusion injury due to reduced numbers of resident CD4+ T cells
Liver grafts from CD39-overexpressing rodents are protected from ischemia reperfusion injury due to reduced numbers of resident CD4+ T cells
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DOI：
10.1002/hep.25985
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发表时间：
2013-04-01
期刊：
影响因子：
13.5
通讯作者：
Dwyer, Karen M.
中科院分区：
文献类型：
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作者：
Pommey, Sandra;Lu, Bo;Dwyer, Karen M.
缺血再灌注损伤 (IRI) 是成功肝移植的主要限制事件，CD4+ T 细胞和不变自然杀伤 T (iNKT) 细胞与促进 IRI 有关。我们假设肝脏过度表达CD39（一种具有抗炎功能的核酸外切酶）将在长期冷缺血后保护肝移植物。 CD39转基因（CD39tg）和野生型（WT）小鼠肝脏冷藏18小时后移植到WT受体中，移植后6小时进行病理分析。与WT肝脏的受者相比，CD39tg肝脏的受者的丙氨酸氨基转移酶和白细胞介素(IL)-6的血清水平显着降低。此外，CD39tg 移植物中的组织病理学损伤较轻。免疫分析显示，未经治疗的 CD39tg 小鼠肝脏中 CD4+ T 细胞和 iNKT 细胞的数量显着减少。这与胸腺细胞成熟缺陷导致的外周 CD4+ T 细胞淋巴细胞减少有关。为了评估肝脏驻留的 CD4+ T 细胞和 iNKT 细胞在介导长期冷藏和移植后肝损伤中的相对重要性，使用耗尽 CD4+ T 细胞的 WT 小鼠或 iNKT 细胞遗传缺陷的小鼠作为供体。 CD4+ T 细胞（而非 iNKT 细胞）的缺失可以保护肝移植物免受早期 IRI 的影响。结论：肝脏 CD4+ T 细胞（而非 iNKT 细胞）在肝移植模型中长期冷藏后的早期 IRI 中发挥着关键作用。 （肝病学 2013）
Ischemia-reperfusion injury (IRI) is a major limiting event for successful liver transplantation, and CD4+ T cells and invariant natural killer T (iNKT) cells have been implicated in promoting IRI. We hypothesized that hepatic overexpression of CD39, an ectonucleotidase with antiinflammatory functions, will protect liver grafts after prolonged cold ischemia. CD39-transgenic (CD39tg) and wildtype (WT) mouse livers were transplanted into WT recipients after 18 hours cold storage and pathological analysis was performed 6 hours after transplantation. Serum levels of alanine aminotransferase and interleukin (IL)-6 were significantly reduced in recipients of CD39tg livers compared to recipients of WT livers. Furthermore, less severe histopathological injury was demonstrated in the CD39tg grafts. Immune analysis revealed that CD4+ T cells and iNKT cells were significantly decreased in number in the livers of untreated CD39tg mice. This was associated with a peripheral CD4+ T cell lymphopenia due to defective thymocyte maturation. To assess the relative importance of liver-resident CD4+ T cells and iNKT cells in mediating liver injury following extended cold preservation and transplantation, WT mice depleted of CD4+ T cells or mice genetically deficient in iNKT cells were used as donors. The absence of CD4+ T cells, but not iNKT cells, protected liver grafts from early IRI. Conclusion: Hepatic CD4+ T cells, but not iNKT cells, play a critical role in early IRI following extended cold preservation in a liver transplant model. (HEPATOLOGY 2013)