NKp80 defines and stimulates a reactive subset of CD8 T cells
NKp80 defines and stimulates a reactive subset of CD8 T cells
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DOI：
10.1182/blood-2008-03-145615
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发表时间：
2009-01-08
期刊：
影响因子：
20.3
通讯作者：
Steinle, Alexander
中科院分区：
文献类型：
--
作者：
Kuttruff, Sabrina;Koch, Sven;Steinle, Alexander
NKp80是一种激活的同源二聚体C型凝集素样受体(CTLR)，在几乎所有的人类自然杀伤(NK)细胞上都有表达，并刺激其细胞毒作用和细胞因子的释放。最近，我们证实NKp80的配体是髓系特异性CTLR激活诱导的C型凝集素(AICL)，它编码在NKp80附近的自然杀伤基因复合体(NKC)中。在这里，我们发现NKp80也表达在人类CD8T细胞的一小部分上，表现出高反应性和效应记忆表型。基因表达谱分析和流式细胞仪分析表明，这个NKp80(+)T细胞亚群的特征是与其他NK受体共表达，以及介导炎症部位进入的细胞毒效应分子和黏附分子水平增加。NKp80结扎可增加CD3刺激的效应记忆T细胞脱颗粒和干扰素(干扰素)γ的分泌。此外，在异体反应环境中，表达AICL的转染者或巨噬细胞与NKp80的结合显著增强了CD8T细胞的反应。总之，我们的数据表明，NKp80表达在具有炎症性NK样表型的效应记忆CD8T细胞上，并促进T细胞对AICL表达细胞的反应。因此，NKp80可能使效应记忆CD8 T细胞在炎症部位与髓系细胞发生功能性相互作用。(血。2009；113：358-369)
NKp80, an activating homodimeric C-type lectin-like receptor (CTLR), is expressed on essentially all human natural killer (NK) cells and stimulates their cytotoxicity and cytokine release. Recently, we demonstrated that the ligand for NKp80 is the myeloid-specific CTLR activation-induced C-type lectin (AICL), which is encoded in the natural killer gene complex (NKC) adjacent to NKp80. Here, we show that NKp80 also is expressed on a minor fraction of human CD8 T cells that exhibit a high responsiveness and an effector memory phenotype. Gene expression profiling and flow cytometric analyses revealed that this NKp80(+) T-cell subset is characterized by the coexpression of other NK receptors and increased levels of cytotoxic effector molecules and adhesion molecules mediating access to sites of inflammation. NKp80 ligation augmented CD3-stimulated degranulation and interferon (IFN)gamma secretion by effector memory T cells. Furthermore, engagement of NKp80 by AICL-expressing transfectants or macrophages markedly enhanced CD8 T-cell responses in alloreactive settings. Collectively, our data demonstrate that NKp80 is expressed on a highly responsive subset of effector memory CD8 T cells with an inflammatory NK-like phenotype and promotes T-cell responses toward AICL-expressing cells. Hence, NKp80 may enable effector memory CD8 T cells to interact functionally with cells of myeloid origin at sites of inflammation. (Blood. 2009;113:358-369)