Lange A, Ernst M, Jaźwiec B, Ennen J, Flad H D
Borstel Research Institute, FRG.
Nat Immun Cell Growth Regul. 1987;6(5):237-49.
Peripheral blood low-density cells were sorted, with respect to their ability to accumulate the lysosomotropic agent mepacrine (Mep), into lysosome-rich (Mep+) and lysosome-poor (Mep-) cell populations. Cells of large granular lymphocyte (LGL) morphology and phenotype were found in the Mep+ but not in the Mep- cell population. The latter cells lacked any natural killer (NK) activity. Cultures of the Mep- cells resulted in the appearance of cells showing K-562 lytic activity, LGL morphology and CD16 and/or Leu-7 positivity. This process was facilitated by the supplementation of the culture with recombinant human interleukin-2 (rIL-2). Mep+ cells retested after 7 days of culture showed a decline in the fraction of granular (LGL and Mep+) cells. This decrease was less pronounced but also seen in rIL-2-supplemented cultures. In spite of the lower number of typical LGL, Mep+ cells cultured with rIL-2 were mostly large but scarcely granular; rIL-2-activated K-562 killing (rIL-2 AK) of originally Mep+ cells was much higher than K-562 lytic activity of these cells at the beginning of the culture, and as compared to rIL-2 AK of Mep- cells. From this finding it is apparent that the most active rIL-2 AK cells originate from low-density granular (Mep+) cells (LGL) and, therefore, we propose to call them 'giant' NK cells. Furthermore, in the presence of rIL-2, LGL differentiate from agranular (Mep-) low-density cells. In view of these data, LGL appear to be resting cells on the differentiation pathway of NK cells.
外周血低密度细胞根据其积累溶酶体亲和剂米帕林（Mep）的能力，被分选成富含溶酶体的（Mep+）和溶酶体含量低的（Mep-）细胞群体。在Mep+细胞群体中发现了具有大颗粒淋巴细胞（LGL）形态和表型的细胞，而在Mep-细胞群体中未发现。后者细胞缺乏任何自然杀伤（NK）活性。Mep-细胞培养物中出现了显示K-562裂解活性、LGL形态以及CD16和/或Leu-7阳性的细胞。用重组人白细胞介素-2（rIL-2）补充培养可促进这一过程。培养7天后重新检测的Mep+细胞显示，颗粒状（LGL和Mep+）细胞的比例下降。这种下降在补充rIL-2的培养物中不太明显，但也能观察到。尽管典型LGL数量较少，但用rIL-2培养的Mep+细胞大多体积大但颗粒稀少；与培养开始时这些细胞的K-562裂解活性相比，以及与Mep-细胞的rIL-2激活的K-562杀伤（rIL-2 AK）相比，原来Mep+细胞的rIL-2 AK要高得多。从这一发现可以明显看出，最活跃的rIL-2 AK细胞起源于低密度颗粒状（Mep+）细胞（LGL），因此，我们建议将它们称为“巨型”NK细胞。此外，在rIL-2存在的情况下，LGL从无颗粒的（Mep-）低密度细胞分化而来。鉴于这些数据，LGL似乎是NK细胞分化途径上的静止细胞。
