Ellis T M, Creekmore S P, McMannis J D, Braun D P, Harris J A, Fisher R I
Section of Hematology/Oncology, Loyola University Stritch School of Medicine, Maywood, Illinois 60153.
Cancer Res. 1988 Nov 15;48(22):6597-602.
The effects of recombinant interleukin 2 (rIL-2) therapy on peripheral blood mononuclear cells expressing the Leu 19 surface marker were evaluated in 20 cancer patients. Leu 19 is a protein with a molecular weight of 220,000 expressed on 15% of normal peripheral blood mononuclear cells and is found on a majority of cells that mediate non-major histocompatibility complex-restricted cytotoxicity. Increased relative and absolute numbers of circulating Leu 19+ cells were observed in all patients receiving rIL-2. Increases in Leu 19+ cells were due in part to the development of a subpopulation of "bright" Leu 19+ cells (Leu 19b+) that possessed a higher density of membrane Leu 19 antigen than Leu 19+ cells assayed prior to therapy. Further characterization of rIL-2 induced Leu 19+ cells by dual immunofluorescence revealed considerable phenotypic heterogeneity within this population based on the coexpression of "dim" CD8 (CD8d+), CD16, and CD2 markers. The percentage of Leu 19+ CD8d+ cells was increased during rIL-2 therapy and comprised up to 60% of all circulating Leu 19+ cells. CD16+ and CD16- subsets of Leu 19+ cells were also increased by rIL-2. The density of CD16 antigen coexpression varied inversely with the density of Leu 19. Conversely, whereas the percentage of Leu 19 cells coexpressing CD2 was also increased by rIL-2 administration, the density of CD2 antigen expression was higher on the Leu 19b+ subset of cells. The development of circulating lymphokine-activated killer activity in three patients was temporally associated with the development of increased levels of circulating Leu 19+ cells. These studies demonstrate that rIL-2 administration induces preferential increases in cells expressing the natural killer and lymphokine-activated killer cell-associated marker Leu 19 and that these increases are associated with the development of circulating lymphokine-activated killer activity. Furthermore, Leu 19+ cells are comprised of phenotypically heterogeneous subsets which undergo characteristic changes during rIL-2 administration.
在20例癌症患者中评估了重组白细胞介素2（rIL-2）治疗对表达Leu 19表面标志物的外周血单个核细胞的影响。Leu 19是一种分子量为220,000的蛋白质，在15%的正常外周血单个核细胞上表达，并且在大多数介导非主要组织相容性复合体限制的细胞毒性的细胞上发现。在所有接受rIL-2治疗的患者中均观察到循环Leu 19+细胞的相对数量和绝对数量增加。Leu 19+细胞的增加部分归因于“明亮的”Leu 19+细胞（Leu 19b+）亚群的出现，该亚群的膜Leu 19抗原密度高于治疗前检测的Leu 19+细胞。通过双重免疫荧光对rIL-2诱导的Leu 19+细胞进行进一步表征，发现基于“暗淡的”CD8（CD8d+）、CD16和CD2标志物的共表达，该群体内存在相当大的表型异质性。在rIL-2治疗期间，Leu 19+ CD8d+细胞的百分比增加，占所有循环Leu 19+细胞的60%。rIL-2也增加了Leu 19+细胞的CD16+和CD16-亚群。CD16抗原共表达的密度与Leu 19的密度呈负相关。相反，虽然给予rIL-2也增加了共表达CD2的Leu 19细胞的百分比，但CD2抗原在Leu 19b+细胞亚群上的表达密度更高。3例患者循环淋巴因子激活的杀伤活性的出现与循环Leu 19+细胞水平升高在时间上相关。这些研究表明，给予rIL-2可诱导表达自然杀伤和淋巴因子激活的杀伤细胞相关标志物Leu 19的细胞优先增加，并且这些增加与循环淋巴因子激活的杀伤活性的出现相关。此外，Leu 19+细胞由表型异质的亚群组成，在给予rIL-2期间经历特征性变化。
