Appearance and phenotypic characterization of circulating Leu 19+ cells in cancer patients receiving recombinant interleukin 2.
Appearance and phenotypic characterization of circulating Leu 19+ cells in cancer patients receiving recombinant interleukin 2.
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发表时间：
1988-11
期刊：
影响因子：
11.2
通讯作者：
T. Ellis;S. Creekmore;J. McMannis;D. Braun;J. A. Harris;R. Fisher
中科院分区：
文献类型：
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作者：
T. Ellis;S. Creekmore;J. McMannis;D. Braun;J. A. Harris;R. Fisher
对20例恶性肿瘤患者外周血单个核细胞表面标记物Leu 19进行了重组白细胞介素2（rIL-2）治疗。Leu 19是一种分子量为220，000的蛋白质，在15%的正常外周血单核细胞上表达，并且在大多数介导非主要组织相容性复合物限制性细胞毒性的细胞上发现。在接受rIL-2的所有患者中观察到循环Leu 19+细胞的相对和绝对数量增加。Leu 19+细胞的增加部分是由于“亮”Leu 19+细胞（Leu 19 b+）亚群的发育，其具有比治疗前测定的Leu 19+细胞更高的膜Leu 19抗原密度。通过双重免疫荧光进一步表征rIL-2诱导的Leu 19+细胞揭示了基于“暗淡”CD 8（CD 8d+）、CD 16和CD 2标记物的共表达的该群体内相当大的表型异质性。Leu 19+ CD 8d+细胞的百分比在rIL-2治疗期间增加，并且占所有循环Leu 19+细胞的高达60%。rIL-2还可增加Leu 19+细胞的CD 16+和CD 16-亚群。CD 16抗原共表达的密度与Leu 19的密度成反比。相反，尽管共表达CD 2的Leu 19细胞的百分比也通过rIL-2给药而增加，但在Leu 19 b+细胞亚群上CD 2抗原表达的密度更高。在3例患者中，循环淋巴因子激活的杀伤活性的发展与循环Leu 19+细胞水平升高的发展存在时间相关性。这些研究表明，rIL-2给药诱导表达自然杀伤细胞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细胞活性的发展相关。此外，Leu 19+细胞由在rIL-2给药期间经历特征性变化的表型异质亚群组成。
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.