Hsieh Christine L, Nagasaki Kazuhito, Martinez Olivia M, Krams Sheri M
Department of Surgery, Division of Transplantation and Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305-5492, USA.
Eur J Immunol. 2006 Aug;36(8):2170-80. doi: 10.1002/eji.200635982.
NKp30 is a stimulatory receptor on human NK cells implicated in tumor immunity, and is capable of promoting or terminating dendritic cell maturation. To gain a better understanding of NKp30 biology, we have investigated the expression and function of rat NKp30 (rNKp30). We generated stable transfectants of rNKp30 in RNK16 cells, a rat NK lymphoma line, and used a novel panel of mAb against rNKp30 to study this receptor. Using agonistic rNKp30 mAb, we demonstrated that rNKp30 mediates robust IFN-gamma production and cytolytic responses from rNKp30-transfected RNK16 cells. We determined by flow cytometry that rNKp30 is expressed by a subset of primary NK cells isolated from the blood and spleen, and to a lesser extent also on liver NK cells. Stimulation of rNKp30 on primary NK cells led to IFN-gamma production. Liver NK cells expressed low levels of NKp30 and had reduced rNKp30-mediated IFN-gamma responses. During an alloimmune response in vivo, the proportion of the rNKp30(+) NK cell subset in the peripheral blood significantly increased, suggesting that rNKp30 may play an important role during alloactivation. Thus, our data demonstrate that NKp30 is indeed expressed in rodents and is a functional stimulatory receptor in a subset of rat NK cells.
NKp30是人类自然杀伤(NK)细胞上的一种刺激性受体,与肿瘤免疫有关,并且能够促进或终止树突状细胞的成熟。为了更好地理解NKp30的生物学特性,我们研究了大鼠NKp30(rNKp30)的表达和功能。我们在大鼠NK淋巴瘤细胞系RNK16中构建了rNKp30的稳定转染细胞,并使用一组新型的抗rNKp30单克隆抗体(mAb)来研究该受体。使用激动性rNKp30 mAb,我们证明rNKp30介导了来自rNKp30转染的RNK16细胞的强大干扰素-γ(IFN-γ)产生和细胞溶解反应。我们通过流式细胞术确定,rNKp30由从血液和脾脏中分离的原代NK细胞亚群表达,在肝脏NK细胞上的表达程度较低。刺激原代NK细胞上的rNKp30会导致IFN-γ产生。肝脏NK细胞表达低水平的NKp30,并且rNKp30介导的IFN-γ反应减弱。在体内同种异体免疫反应期间,外周血中rNKp30(+) NK细胞亚群的比例显著增加,表明rNKp30可能在同种异体激活过程中发挥重要作用。因此,我们的数据表明NKp30确实在啮齿动物中表达,并且是大鼠NK细胞亚群中的一种功能性刺激性受体。