Frey M, Packianathan N B, Fehniger T A, Ross M E, Wang W C, Stewart C C, Caligiuri M A, Evans S S
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
J Immunol. 1998 Jul 1;161(1):400-8.
NK cells are the first line of defense against foreign cells, virally infected cells, and tumors. The mechanisms whereby NK cells accumulate in extralymphoid sites in response to pathogenic stimuli are not well understood. The L-selectin adhesion molecule (CD62L) plays a primary role in mediating the initial interaction of leukocytes with vascular endothelium, a crucial step in the extravasation of immune effector cells into tissues. In this report, we show L-selectin to be uniquely expressed on a subset of resting human NK cells (CD56bright). Notably, CD56bright NK cells expressed L-selectin at a higher density than all other peripheral blood leukocytes. NK activation by PMA, IL-2, IL-15, or TGF-beta down-regulated L-selectin on the CD56bright subset, while increased L-selectin levels were observed in both the CD56bright and CD56dim NK subsets in response to IL-12, IL-10, or IFN-alpha. Moreover, CD56bright NK cells bound with high efficiency to physiologic L-selectin ligands on peripheral lymph node high endothelial venules (HEV). In sharp contrast, CD56dim NK cells adhered poorly to HEV and were predominantly L-selectin- or expressed L-selectin only at low density. In CD56bright cells and a subpopulation of CD56dim cells, L-selectin ligation by mAb cross-linking activated lymphocyte function-associated Ag 1 (LFA-1), a second adhesion molecule required for leukocyte extravasation. LFA-1 was expressed on both NK subsets, although its density was constitutively higher on CD56dim cells. Taken together, evidence of differential expression of L-selectin and LFA-1 on CD56bright and CD56dim NK subsets strongly suggests unique migratory properties and functions of these cells during the early immune response to foreign pathogens.
自然杀伤细胞（NK细胞）是抵御外来细胞、病毒感染细胞和肿瘤的第一道防线。目前对于NK细胞在致病刺激下积聚于淋巴外部位的机制尚不清楚。L-选择素黏附分子（CD62L）在介导白细胞与血管内皮的初始相互作用中起主要作用，这是免疫效应细胞渗出到组织中的关键步骤。在本报告中，我们发现L-选择素在静息人NK细胞（CD56bright）的一个亚群上独特表达。值得注意的是，CD56bright NK细胞表达L-选择素的密度高于所有其他外周血白细胞。佛波酯（PMA）、白细胞介素-2（IL-2）、白细胞介素-15（IL-15）或转化生长因子-β（TGF-β）激活NK细胞会下调CD56bright亚群上的L-选择素，而在CD56bright和CD56dim NK亚群中，白细胞介素-12（IL-12）、白细胞介素-10（IL-10）或干扰素-α（IFN-α）可使L-选择素水平升高。此外，CD56bright NK细胞能高效结合外周淋巴结高内皮微静脉（HEV）上的生理性L-选择素配体。与之形成鲜明对比的是，CD56dim NK细胞与HEV的黏附性很差，且主要不表达L-选择素或仅低密度表达L-选择素。在CD56bright细胞和一部分CD56dim细胞中，单克隆抗体交联L-选择素可激活淋巴细胞功能相关抗原1（LFA-1），这是白细胞渗出所需的第二种黏附分子。两个NK亚群均表达LFA-1，尽管其密度在CD56dim细胞上本底较高。综上所述，CD56bright和CD56dim NK亚群上L-选择素和LFA-1的差异表达证据强烈表明，在对外来病原体的早期免疫反应中，这些细胞具有独特的迁移特性和功能。
