Bcl-xL is associated with the anti-apoptotic effect of IL-15 on the survival of CD56dim natural killer cells
Bcl-xL is associated with the anti-apoptotic effect of IL-15 on the survival of CD56dim natural killer cells
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DOI：
10.1016/j.molimm.2008.01.001
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发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
--
作者：
Zheng, Xiaodong;Wang, Yanyan;Tian, Zhigang
人NK细胞可以基于细胞表面CD 56密度区分为CD 56（亮）和CD 56（暗）亚群。研究表明，IL-2和IL-15对CD 8（+）T细胞的生存和死亡具有相反的作用。然而，IL-2和IL-15在调节这两种NK细胞亚群中的作用仍然难以捉摸。本研究比较分析了IL-2和IL-15对两种NK细胞亚群的影响。IL-15可促进CD 56（dim）NK细胞在脐血单个核细胞长期培养中的增殖和活化，而IL-2仅维持CD 56亮NK细胞的存活。IL-15培养的CD 56（+）Annexin V+ NK细胞的百分比低于IL-2培养的CD 56（+）Annexin V+ NK细胞的百分比，并且Annexin V+ NK细胞主要存在于CD 56（dim）NK细胞中。IL-15培养的NK细胞比IL-2培养的NK细胞表达更高水平的Bcl-xL。此外，与IL-2相比，IL-15更强烈地上调CD 25表达并更好地维持IL-15 R α的表达。这些结果表明，当与IL-2一起培养时，CD 56（dim）NK细胞经历凋亡，但IL-15抑制其凋亡，并且Bcl-xL与IL-15的抗凋亡作用相关。因此，IL-15在维持CD 56（dim）NK细胞的长期功能中起着至关重要的作用。(C)2008爱思唯尔有限公司保留所有权利。
Human NK cells can be distinguished into CD56(bright) and CD56(dim) subsets based on cell surface CD56 density. It has been shown that IL-2 and IL-15 have opposing effects on life and death of CD8(+) T cells. However, the roles of IL-2 and IL-15 in regulating these two NK cell subsets remain elusive. In this study, we comparatively analyzed the effects of IL-2 and IL-15 on two NK cell subsets. IL-15 improved the proliferation and activation of CD56(dim) NK cells in long-term cord blood mononuclear cell culture, but IL-2 only maintained the survival of CD56 bright NK cells. The percentage of CD56(+) Annexin V+ NK cells cultured with IL-15 was lower than that with IL-2; moreover, most of Annexin V+ NK cells were primarily in the CD56(dim) NK cells. IL-15 cultured NK cells expressed higher level of Bcl-xL than IL-2 cultured cells. Furthermore, IL-15 more strongly upregulated CD25 expression and better maintained the expression of IL-15R alpha than IL-2. These results suggest that CD56(dim) NK cells undergo apoptosis when cultured with IL-2, but IL-15 inhibits their apoptosis and Bcl-xL is associated with the anti-apoptotic effect of IL-15. So IL-15 played a crucial role in sustaining long-lasting functions of CD56(dim) NK cells. (C) 2008 Elsevier Ltd. All rights reserved.