Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation
Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation
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DOI：
10.1053/he.2000.5850
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发表时间：
2000-04-01
期刊：
影响因子：
13.5
通讯作者：
Abo, T
中科院分区：
文献类型：
--
作者：
Minagawa, M;Oya, H;Abo, T
C57BL/6小鼠肝部分切除(PHX)后，在肝细胞再生早期(PHX后4~12小时)，肝脏出现严重的淋巴细胞增多症。在这个器官中扩张的一个主要淋巴细胞亚群估计是自然杀伤1.1(+)(NK1.1(+))中间CD3(INT)细胞(即NKT细胞)。CD3(Int)细胞是原位产生于肝脏的胸腺外T细胞。当用β-肾上腺素能D拮抗剂(即，β-受体阻滞剂)心得安(PPL)预先处理PHX小鼠时，这些变化被抑制。这可能是由肝细胞再生过程中的交感神经刺激引起的。一种α-受体阻滞剂显示了类似的作用，尽管抑制程度比β-受体阻滞剂低，但我们以前发现NK和NKT细胞表达表面β-肾上腺素能受体，并被交感神经刺激激活。在本研究中，PHX小鼠肝淋巴细胞介导的NK细胞杀伤活性降低，而NKT对同基因胸腺细胞的杀伤活性增加。纯化的CD3(Int)细胞也能介导NKT对再生肝细胞的杀伤作用。这些结果表明，PHX后刺激交感神经可导致NKT细胞的激活，这些NKT细胞可能与肝细胞再生过程中的免疫监测有关。
When C57BL/6 mice were partially hepatectomized (PHx), severe lymphocytosis was induced in the liver in the early phase of hepatocyte regeneration (4 to 12 hours after PHx). A major lymphocyte subset expanding in this organ was estimated to be natural killer 1.1(+) (NK1.1(+)) intermediate CD3 (CD3(int)) cells (i.e., NKT cells). CD3(int) cells are extrathymic T cells generated in situ in the liver. These changes were suppressed when mice with PHx were pretreated with a beta-adrenergicD antagonist (i.e., beta-blocker), propranolol (PPL). This might have been caused by sympathetic nerve stimulation during hepatocyte regeneration. An alpha-blocker showed a similar effect, although the magnitude of suppression was lower than that of the beta-blocker, We previously showed that NK and NKT cells express surface beta-adrenergic receptors and are activated in number by sympathetic nerve stimulation. In the present study, NK cytotoxicity mediated by liver lymphocytes obtained from mice with PHx decreased, whereas NKT cytotoxicity against syngeneic thymocytes increased. Purified CD3(int) cells were also found to be able to mediate NKT cytotoxicity against regenerating hepatocytes. These results suggest that sympathetic nerve stimulation after PHx results in subsequent activation of NKT cells and that these NKT cells might be associated with immunologic surveillance during hepatocyte regeneration.