Richards James A, Wigmore Stephen J, Anderton Stephen M, Howie Sarah E M
MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK; Clinical Surgery, The University of Edinburgh, Edinburgh, UK.
MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK; Clinical Surgery, The University of Edinburgh, Edinburgh, UK.
Transpl Immunol. 2017 Dec;45:15-21. doi: 10.1016/j.trim.2017.08.002. Epub 2017 Aug 7.
IRI results from the interruption then reinstatement of an organ's blood supply, and this poses a significant problem in liver transplantation and resectional surgery. In this paper, we explore the role T cells play in the pathogenesis of this injury.
MATERIALS & METHODS: We used an in vivo murine model of warm partial hepatic IRI, genetically-modified mice, in vivo antibody depletion, adoptive cell transfer and flow cytometry to determine which lymphocyte subsets contribute to pathology. Injury was assessed by measuring serum alanine aminotransfersase (ALT) and by histological examination of liver tissue sections.
The absence of T cells (CD3εKO) is associated with significant protection from injury (p=0.010). Through a strategy of antibody depletion it appears that NKT cells (p=0.0025), rather than conventional T (CD4+ or CD8+) (p=0.11) cells that are the key mediators of injury.
Our results indicate that tissue-resident NKT cells, but not other lymphocyte populations are responsible for the injury in hepatic IRI. Targeting the activation of NKT cells and/or their effector apparatus would be a novel approach in protecting the liver during transplantation and resection surgery; this may allow us to expand our current criteria for surgery.
缺血再灌注损伤（IRI）源于器官血液供应的中断然后恢复，这在肝移植和肝切除手术中是一个重大问题。在本文中，我们探讨了T细胞在这种损伤发病机制中所起的作用。
我们使用了一种温性部分肝IRI的体内小鼠模型、基因改造小鼠、体内抗体清除、过继性细胞转移和流式细胞术来确定哪些淋巴细胞亚群导致病理变化。通过测量血清丙氨酸转氨酶（ALT）以及对肝组织切片进行组织学检查来评估损伤情况。
T细胞缺失（CD3ε基因敲除小鼠）与显著的损伤保护相关（p = 0.010）。通过抗体清除策略发现，自然杀伤T细胞（p = 0.0025）而非传统T细胞（CD4⁺或CD8⁺）（p = 0.11）是损伤的关键介质。
我们的结果表明，组织驻留自然杀伤T细胞而非其他淋巴细胞群体是肝IRI损伤的原因。针对自然杀伤T细胞的激活及其效应器可能是在移植和切除手术中保护肝脏的一种新方法；这可能使我们能够扩大当前的手术标准。
