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重组人白细胞介素2体外增强自然杀伤细胞活性的方式:脐血和成人外周血中Leu-11 +和Leu-11-细胞群的比较研究

Mode of in vitro augmentation of natural killer cell activity by recombinant human interleukin 2: a comparative study of Leu-11+ and Leu-11- cell populations in cord blood and adult peripheral blood.

作者信息

Seki H, Ueno Y, Taga K, Matsuda A, Miyawaki T, Taniguchi N

出版信息

J Immunol. 1985 Oct;135(4):2351-6.

PMID:3928745
Abstract

Human newborn natural killer (NK) cell activity against K562 target cells was observed to be low compared with adult controls. Although Leu-7 (HNK-1)+ cells were negligible in cord blood, the proportions of Leu-11+ cells were equal to those of adult peripheral blood. Leu-11+ cells sorted from cord blood lymphocytes, as well as from adult lymphocytes exhibited the morphology of granular lymphocytes. In this study, we have investigated the phenotypic characterization of recombinant interleukin 2 (rIL 2)-induced cytotoxic lymphocytes against K562 cells by using anti-Leu-11 monoclonal antibody. Spontaneous cytotoxicity of lymphocytes was restricted to Leu-11+ cells in cord blood, as well as in adult blood, but this activity was low in cord blood Leu-11+ cells as compared with that of adult ones. NK cell activity of adult Leu-11+ cells could not be additionally enhanced after an 18-hr incubation with rIL 2(25 U/ml), whereas rIL 2 could potentiate the cytotoxicity of cord blood Leu-11+ cells approximately to the adult levels. It should be noted that cytotoxic activity of both Leu-11- cells from cord blood and adult blood that had no basal NK cells activity could be significantly potentiated by rIL 2. On the other hand, lymphokine-activated killer cells cytotoxic for HL-60 cell line could not be generated, and no proliferation of the lymphocytes was detected after an 18-hr incubation with rIL 2. It was shown that rIL 2 could not enhance the ability to bind to target cells in Leu-11+ and Leu-11- cells by means of a single cell conjugate assay, but the rate of target lysis of Leu-11+ cells from cord blood was significantly enhanced by rIL 2. These results suggested that rIL 2-induced cytotoxic effector cells were heterogeneous, and rIL 2 might potentiate the cytotoxicity of functionally immature NK cells or NK precursor cells.

摘要

与成年对照组相比,观察到人类新生儿自然杀伤(NK)细胞对K562靶细胞的活性较低。尽管脐带血中Leu-7(HNK-1)+细胞可忽略不计,但Leu-11+细胞的比例与成人外周血中的比例相当。从脐带血淋巴细胞以及成人淋巴细胞中分选出来的Leu-11+细胞呈现出颗粒淋巴细胞的形态。在本研究中,我们使用抗Leu-11单克隆抗体研究了重组白细胞介素2(rIL 2)诱导的针对K562细胞的细胞毒性淋巴细胞的表型特征。淋巴细胞的自发细胞毒性在脐带血和成人血液中均局限于Leu-11+细胞,但与成人的Leu-11+细胞相比,脐带血中Leu-11+细胞的这种活性较低。成年Leu-11+细胞与rIL 2(25 U/ml)孵育18小时后,其NK细胞活性无法进一步增强,而rIL 2可将脐带血Leu-11+细胞的细胞毒性增强至接近成人水平。应当指出的是,脐带血和成人血液中原本无基础NK细胞活性的Leu-11-细胞的细胞毒性活性均可被rIL 2显著增强。另一方面,无法产生对HL-60细胞系具有细胞毒性的淋巴因子激活的杀伤细胞,且与rIL 2孵育18小时后未检测到淋巴细胞增殖。结果表明,rIL 2不能通过单细胞结合试验增强Leu-11+和Leu-11-细胞与靶细胞结合的能力,但rIL 2可显著增强脐带血Leu-11+细胞的靶细胞裂解率。这些结果表明,rIL 2诱导的细胞毒性效应细胞是异质性的,rIL 2可能增强功能不成熟的NK细胞或NK前体细胞的细胞毒性。

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