Nakazawa T, Agematsu K, Yabuhara A
Department of Paediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Immunology. 1997 Oct;92(2):180-7. doi: 10.1046/j.1365-2567.1997.00343.x.
We classified CD56+ CD3- natural killer (NK) cells into CD2- CD56dim (CD2- NK), CD2+ CD56dim (CD2+ NK) and CD2+ CD56bright populations, and investigated mainly functional differences between the former two populations. CD2- and CD2+ NK cells were the same in their morphology and several surface molecules except for CD2. The percentages of CD2- NK cells in total NK cells were higher in the cord blood and marrow than in the peripheral blood of adults or children. Freshly isolated CD2- NK cells had CD2 in the cytoplasm, and gradually expressed it on the surface upon incubation with interleukin-2 (IL-2). These results demonstrated that CD2 is an antigen which appears on the surface during the maturation of NK cells. The granule-mediated cytotoxicities, which are mainly performed by the perforin molecule, of CD2+ NK cells against K562 and Daudi cells were higher than those of CD2- NK cells, and they were inhibited to the levels of CD2- NK cells by the addition of a blocking anti-CD2 monoclonal antibody (mAb). Fas ligand (FasL) mRNA was expressed in freshly isolated CD2+ NK cells but not in the CD2- NK cells. Neither freshly isolated NK populations showed FasL-mediated cytotoxicity, and only CD2+ NK cells lysed Fas-transfected targets after the 24-hr incubation with IL-2. Based on these results, CD2- NK cells have already developed granule-mediated cytotoxicity equal to that of CD2+ NK cells except for the CD2-associated activity, but they, unlike CD2+ NK cells, totally lack FasL-mediated cytotoxicity. These findings suggest that FasL-mediated cytotoxicity may be acquired at more mature stages of NK-cell maturation than granule-mediated cytotoxicity.
我们将CD56+ CD3-自然杀伤(NK)细胞分为CD2- CD56dim(CD2- NK)、CD2+ CD56dim(CD2+ NK)和CD2+ CD56bright亚群,并主要研究了前两个亚群之间的功能差异。CD2-和CD2+ NK细胞在形态和除CD2外的几种表面分子方面相同。脐带血和骨髓中CD2- NK细胞在总NK细胞中的百分比高于成人或儿童外周血中的百分比。新鲜分离的CD2- NK细胞在细胞质中有CD2,并在与白细胞介素-2(IL-2)孵育后逐渐在表面表达。这些结果表明CD2是一种在NK细胞成熟过程中出现在表面的抗原。CD2+ NK细胞对K562和Daudi细胞的颗粒介导的细胞毒性(主要由穿孔素分子执行)高于CD2- NK细胞,并且通过添加阻断性抗CD2单克隆抗体(mAb),其细胞毒性被抑制到CD2- NK细胞的水平。Fas配体(FasL)mRNA在新鲜分离的CD2+ NK细胞中表达,但在CD2- NK细胞中不表达。两个新鲜分离的NK亚群均未显示FasL介导的细胞毒性,并且只有CD2+ NK细胞在与IL-2孵育24小时后裂解Fas转染的靶细胞。基于这些结果,CD2- NK细胞除了与CD2相关的活性外,已经具有与CD2+ NK细胞相当的颗粒介导的细胞毒性,但与CD2+ NK细胞不同,它们完全缺乏FasL介导的细胞毒性。这些发现表明,FasL介导的细胞毒性可能在NK细胞成熟的比颗粒介导的细胞毒性更成熟阶段获得。