Jamieson Amanda M, Diefenbach Andreas, McMahon Christopher W, Xiong Na, Carlyle James R, Raulet David H
Department of Molecular and Cell Biology and Cancer Research Laboratory, 489 Life Sciences Addition, University of California, Berkeley, 94720, USA.
Immunity. 2002 Jul;17(1):19-29. doi: 10.1016/s1074-7613(02)00333-3.
Little is known concerning the stimulatory receptors responsible for tumor cell lysis by NK cells. We generated a monoclonal antibody specific for murine NKG2D in order to investigate its function. Blocking of NKG2D inhibited natural cytotoxicity of all tumor cells tested that express ligands for the receptor. Staining analysis showed that NKG2D is also expressed by activated CD8(+) T cells and macrophages, and subsets of TCRgammadelta(+) and NK1.1(+) T cells. Contradicting reports that NKG2D is solely a costimulatory receptor, we observed that cross-linking of NKG2D directly stimulates NK cells and activated macrophages. In contrast, NKG2D costimulates activated CD8(+) T cells. Thus, NKG2D engagement directly stimulates NK cells and macrophages, costimulates CD8(+) T cells, and plays a substantial role in natural killing.
关于负责自然杀伤细胞(NK细胞)介导肿瘤细胞裂解的刺激受体,人们了解甚少。我们制备了一种针对小鼠NKG2D的单克隆抗体,以研究其功能。阻断NKG2D可抑制所有测试的表达该受体配体的肿瘤细胞的自然细胞毒性。染色分析表明,NKG2D也表达于活化的CD8(+) T细胞、巨噬细胞、TCRγδ(+)和NK1.1(+) T细胞亚群。与NKG2D仅是共刺激受体的报道相反,我们观察到NKG2D的交联直接刺激NK细胞和活化的巨噬细胞。相比之下,NKG2D共刺激活化的CD8(+) T细胞。因此,NKG2D的结合直接刺激NK细胞和巨噬细胞,共刺激CD8(+) T细胞,并在自然杀伤中发挥重要作用。