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针对新鲜人白血病细胞的淋巴因子激活杀伤细胞的产生及特性分析

Generation and characterization of lymphokine-activated killer cells against fresh human leukemia cells.

作者信息

Tahara T, Iseki R, Morishima Y, Yokomaku S, Ohno R, Saito H

机构信息

First Department of Internal Medicine, Nagoya University School of Medicine.

出版信息

Jpn J Cancer Res. 1988 Mar;79(3):390-9. doi: 10.1111/j.1349-7006.1988.tb01603.x.

Abstract

Lymphokine-activated killer (LAK) cells generated from 15 acute leukemia patients in remission showed significant levels of cytotoxicity against Daudi 1A4, a natural killer-resistant cell line. This indicates that lymphocytes of leukemia patients in remission could respond to interleukin-2 to generate conventional LAK cells. However, LAK cells caused lysis of autologous leukemia cells at considerably lower levels in seven out of the 15 patients, with the exception of one case (48.6% cytolysis). None of the remaining eight patients exhibited LAK activity against autologous leukemia cells. On the other hand, patients' LAK could lyse allogeneic leukemia cells including those resistant to autologous LAK. Thus, patients' LAK seem not to be defective in lysis of leukemia cells. In the cold target competition analysis, the binding of patients' LAK to leukemia cells could be inhibited by autologous and allogeneic leukemia cell competitors, implying that almost all leukemia cells could be recognized by patients' LAK. Most LAK cells from normal donors showed significant lysis of allogeneic leukemia cells, but some leukemia cells were found to be resistant to lysis. LAK cells against both leukemia cells and Daudi 1A4 were phenotypically heterogenous, and were predominantly observed in the T3- fraction in the precursor phase. In the effector phase, whereas LAK activity against leukemia cells was also predominantly shown in the T cell-depleted fraction, similar levels of LAK activity against Daudi 1A4 were found in both the T cell-depleted and -enriched fractions.

摘要

从15名处于缓解期的急性白血病患者体内产生的淋巴因子激活的杀伤(LAK)细胞,对一种天然杀伤抗性细胞系Daudi 1A4显示出显著水平的细胞毒性。这表明处于缓解期的白血病患者的淋巴细胞能够对白介素-2作出反应,以产生常规的LAK细胞。然而,在15名患者中有7名患者的LAK细胞对自体白血病细胞的裂解水平相当低,其中1例除外(细胞溶解率为48.6%)。其余8名患者均未表现出针对自体白血病细胞的LAK活性。另一方面,患者的LAK细胞能够裂解包括那些对自体LAK有抗性的异基因白血病细胞。因此,患者的LAK细胞在裂解白血病细胞方面似乎没有缺陷。在冷靶竞争分析中,患者的LAK细胞与白血病细胞的结合可被自体和异基因白血病细胞竞争者抑制,这意味着几乎所有白血病细胞都能被患者的LAK细胞识别。来自正常供体的大多数LAK细胞对异基因白血病细胞显示出显著的裂解作用,但发现一些白血病细胞对裂解有抗性。针对白血病细胞和Daudi 1A4的LAK细胞在表型上是异质的,并且在前体阶段主要在T3 - 组分中观察到。在效应阶段,虽然针对白血病细胞的LAK活性也主要在T细胞去除组分中表现出来,但在T细胞去除和富集组分中发现针对Daudi 1A4的LAK活性水平相似。

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