Continuous CD27 triggering in vivo strongly reduces NK cell numbers
Continuous CD27 triggering in vivo strongly reduces NK cell numbers
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DOI：
10.1002/eji.200939251
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发表时间：
2010-04-01
影响因子：
5.4
通讯作者：
Leclercq, Georges
中科院分区：
文献类型：
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作者：
De Colvenaer, Veerle;Taveirne, Sylvie;Leclercq, Georges
NK细胞是早期防御的重要介质。在小鼠中，未成熟和成熟的NK（mNK）细胞组成性表达TNF受体家族成员CD 27;然而，mNK细胞最终失去CD 27表达并成为静息NK细胞。CD 27与其配体CD 70的相互作用增强NK细胞的增殖和效应子功能。我们使用在B细胞上组成性表达CD 70的小鼠（CD 70-Tg）来研究连续触发CD 27对NK细胞的体内作用。持续的CD 70-CD 27相互作用导致NK细胞上的CD 27表达强烈下调，并且NK细胞的绝对数量逐渐减少。这种减少在mNK细胞亚群中最为突出，至少部分是由于细胞凋亡增加。残留的NK细胞显示出较低的活化Ly 49受体表达和正常（肝脏）或减少（脾脏）IFN-γ产生。然而，来自CD 70-Tg小鼠的NK细胞显示出更高的YAC-1杀伤能力。CD 70-Tg NK细胞表现出NKG 2D表达上调，这与YAC-1溶解增加一致，因为这主要是NKG 2D依赖性的。总之，本研究首次证明了体内NK细胞上CD 27的连续CD 70触发导致NK细胞的严重减少。然而，在单细胞的基础上，残留的NK细胞显示出增强的细胞毒性。
NK cells are important mediators of the early defense. In mice, immature and mature NK (mNK) cells constitutively express the TNF receptor family member CD27; however, mNK cells eventually lose CD27 expression and become resting NK cells. Interaction of CD27 with its ligand, CD70, enhances proliferation and effector functions of NK cells. We used mice that constitutively express CD70 on B cells (CD70-Tg) to study the in vivo effects of continuous triggering of CD27 on NK cells. Continuous CD70-CD27 interaction resulted in strongly down-modulated CD27 expression on NK cells and gradually reduced absolute NK cell numbers. This reduction was most prominent in the mNK cell subpopulation and was at least partially due to increased apoptosis. Residual NK cells showed lower expression of activating Ly49 receptors and normal (liver) or decreased (spleen) IFN-gamma production. Nevertheless, NK cells from CD70-Tg mice displayed higher YAC-1 killing capacities. CD70-Tg NK cells exhibited up-regulated expression of NKG2D, which is in accordance with the increased YAC-1 lysis, as this is mainly NKG2D-dependent. Taken together, this study is the first to demonstrate that continuous CD70 triggering of CD27 on NK cells in vivo results in a severe reduction of NK cells. On a single cell basis, however, residual NK cells display enhanced cytotoxicity.