Zarling J M, Kung P C
Nature. 1980 Nov 27;288(5789):394-6. doi: 10.1038/288394a0.
Although it is widely accepted that T cells have a major role in specific tumour immunity, there is now much evidence that natural killer (NK) cells, which exist in many species and spontaneously lyse certain tumour cells in vitro, provide early resistance against tumour growth. Human NK-cell activity can be augmented in vitro by interferon and its inducers, including polyinosinic:polycytidylic acid (poly I:C); furthermore, NK-like activity is generated in mixed leukocyte cultures (MLCs) as is specific cytotoxic T-cell (Tc) activity. When effector cells generated in human MLCs lyse allogeneic or autologous virus-transformed or tumour cells, it has been difficult to evaluate the relative contributions of Tc and NK-like cells to the lysis because the latter, like T cells, can form rosettes with sheep erythrocytes and react with xenogeneic anti-human thymocyte serum. We report here that monoclonal antibodies against human mononuclear cell subpopulations can distinguish Tc from NK and NK-like cells. OKT3 or OKT8 monoclonal antibodies (reactive with virtually all or a subset of T cells, respectively) with complement (C') ablate MLC-generated Tc activity against allogeneic normal cells but do not decrease lysis of HLA-negative, NK-sensitive K562 leukaemia cells by NK, poly I:C-activated NK or MLC-activated NK-like cells. In contrast, OKM1 monoclonal antibody (reactive with a low proportion of non-adherent mononuclear cells as well as macrophages) with C' causes marked diminution of NK and poly I:C-activated NK-cell activity.
尽管人们普遍认为T细胞在特异性肿瘤免疫中起主要作用,但现在有许多证据表明,天然杀伤(NK)细胞存在于许多物种中,在体外能自发裂解某些肿瘤细胞,可提供对肿瘤生长的早期抗性。人NK细胞活性在体外可被干扰素及其诱导剂增强,包括聚肌苷酸:聚胞苷酸(聚I:C);此外,在混合淋巴细胞培养物(MLC)中会产生类似NK的活性,特异性细胞毒性T细胞(Tc)活性也是如此。当在人MLC中产生的效应细胞裂解同种异体或自体病毒转化的或肿瘤细胞时,由于后者与T细胞一样,能与绵羊红细胞形成花环并与异种抗人胸腺细胞血清发生反应,所以很难评估Tc细胞和类似NK细胞对裂解作用的相对贡献。我们在此报告,针对人单核细胞亚群的单克隆抗体可区分Tc细胞与NK细胞及类似NK的细胞。OKT3或OKT8单克隆抗体(分别与几乎所有T细胞或T细胞的一个亚群反应)与补体(C')一起可消除MLC产生的针对同种异体正常细胞的Tc活性,但不会降低NK细胞、聚I:C激活的NK细胞或MLC激活的类似NK细胞对HLA阴性、NK敏感的K562白血病细胞的裂解作用。相比之下,OKM1单克隆抗体(与低比例的非贴壁单核细胞以及巨噬细胞反应)与C'一起会导致NK细胞和聚I:C激活的NK细胞活性显著降低。