Natural killer cell and hepatic cell interaction via NKG2A leads to dendritic cell-mediated induction of CD4+ CD25+ T cells with PD-1-dependent regulatory activities
Natural killer cell and hepatic cell interaction via NKG2A leads to dendritic cell-mediated induction of CD4+ CD25+ T cells with PD-1-dependent regulatory activities
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DOI：
10.1111/j.1365-2567.2006.02479.x
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发表时间：
2007-01-01
期刊：
影响因子：
6.4
通讯作者：
Hayashi, Norio
中科院分区：
文献类型：
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作者：
Jinushi, Masahisa;Takehara, Tetsuo;Hayashi, Norio
自然杀伤 (NK) 细胞能够控制树突状细胞 (DC) 介导的 T 细胞反应。然而，NK 受体介导的 NK 细胞调节决定 DC 介导的 T 细胞反应的幅度和方向的精确机制仍不清楚。在本研究中，我们应用体外共培养系统来研究与肝细胞一起培养的 NK 细胞对 DC 诱导调节性 T 细胞的影响。我们发现，NK 细胞和未转化的肝细胞（表达 HLA-E）通过 NKG2A 抑制性受体相互作用，导致 DC 诱导具有调节特性的 CD4+CD25+T 细胞。 NKG2A 触发导致共培养细胞细胞因子环境的特征性变化；参与这种特定类型 DC 生成的转化生长因子 (TGF)-β 增加，以及能够拮抗 TGF-β 作用的肿瘤坏死因子-α 减少。 NK细胞引发的DC诱导的调节细胞通过负性共刺激程序性死亡1（PD-1）介导的途径发挥抑制作用，这与新鲜分离的CD4（+）CD25（+）T细胞不同。这些发现为 NK 受体信号在 DC 介导的调节性 T 细胞诱导中的作用提供了新的见解。
Natural killer (NK) cells have the ability to control dendritic cell (DC)-mediated T cell responses. However, the precise mechanisms by which NK receptor-mediated regulation of NK cells determines the magnitude and direction of DC-mediated T cell responses remain unclear. In the present study, we applied an in vitro co-culture system to examine the impact of NK cells cultured with hepatic cells on DC induction of regulatory T cells. We found that interaction of NK cells and non-transformed hepatocytes (which express HLA-E) via the NKG2A inhibitory receptor resulted in priming of DCs to induce CD4(+) CD25(+) T cells with regulatory properties. NKG2A triggering led to characteristic changes of the cytokine milieu of co-cultured cells; an increase in the transforming growth factor (TGF)-beta involved in the generation of this specific type of DC, and a decrease in the tumour necrosis factor-alpha capable of antagonizing the effect of TGF-beta. The regulatory cells induced by NK cell-primed DCs exert their suppressive actions through a negative costimulator programmed death-1 (PD-1) mediated pathway, which differs from freshly isolated CD4(+) CD25(+) T cells. These findings provide new insight into the role of NK receptor signals in the DC-mediated induction of regulatory T cells.