Ortaldo J R, Winkler-Pickett R T, Nagata S, Ware C F
Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
J Leukoc Biol. 1997 Feb;61(2):209-15. doi: 10.1002/jlb.61.2.209.
Propriocidal regulation of T cells refers to apoptosis induced by interleukin-2 (IL-2) activation with subsequent antigen receptor stimulation. We previously reported that natural killer (NK) cells also exhibit propriocidal death. Cell death can be induced following occupancy of the Fc gamma RIII (CD16) receptor when NK cells were pretreated with IL-2, IL-12, or IL-15. Here we show other triggering receptors on NK cells such as CD44, anti-NK-receptor antibodies, and pharmacological activation can result in the cell death signal. Requirement for cell interactions indicated that cell contact was required; however, unlike cell-mediated lysis, extracellular calcium was not required. Like T cells, the process of cell death for NK cells was receptor-induced apoptosis. Activation-induced apoptosis of T cells is mediated by members of the tumor necrosis factor (TNF) cytokine superfamily. We examined the involvement of TNF receptor family members or Fas in this rapid cell death. Antibody directed against Fas, TNFR60, TNFR80, LTBR, and LT alpha failed to inhibit receptor-induced death. Therefore, NK cells appear to demonstrate a rapid apoptotic episode when CD16 is cross-linked, but the mechanism of this apoptosis is quite different than was observed in T cells with CD3. The direct examination of the Fas pathway on activated NK cells revealed that susceptibility required longer treatment times and IL-2 activation. This susceptibility was paralleled by increased Fas-ligand expression. Therefore, NK cells can demonstrate an apoptotic response to CD16, CD44, NK receptors, and Fas. The enumeration of ligands capable of eliciting NK cell death and the in vivo relevance of this observation require further study.
T细胞的自毁性调节是指白细胞介素-2（IL-2）激活并随后受到抗原受体刺激所诱导的细胞凋亡。我们之前报道过自然杀伤（NK）细胞也表现出自毁性死亡。当NK细胞用IL-2、IL-12或IL-15预处理后，FcγRIII（CD16）受体被占据时可诱导细胞死亡。在这里我们表明，NK细胞上的其他触发受体，如CD44、抗NK受体抗体和药理学激活，均可导致细胞死亡信号。对细胞相互作用的需求表明需要细胞接触；然而，与细胞介导的裂解不同，细胞外钙并非必需。与T细胞一样，NK细胞的细胞死亡过程是受体诱导的凋亡。T细胞的激活诱导凋亡由肿瘤坏死因子（TNF）细胞因子超家族成员介导。我们研究了TNF受体家族成员或Fas在这种快速细胞死亡中的作用。针对Fas、TNFR60、TNFR80、LTBR和LTα的抗体未能抑制受体诱导的死亡。因此，当CD16交联时，NK细胞似乎表现出快速的凋亡过程，但这种凋亡的机制与CD3刺激的T细胞中观察到的机制有很大不同。对激活的NK细胞上Fas途径的直接检测显示，敏感性需要更长的处理时间和IL-2激活。这种敏感性与Fas配体表达的增加平行。因此，NK细胞可对CD16、CD44、NK受体和Fas表现出凋亡反应。能够引发NK细胞死亡的配体的计数以及这一观察结果在体内的相关性需要进一步研究。
