Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.
Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.
复制标题
淋巴细胞激活的杀伤细胞现象。白细胞介素2个活化的自体外周血淋巴细胞对天然抗杀伤的新鲜实体瘤细胞的裂解。
DOI：
10.1084/jem.155.6.1823
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发表时间：
1982-06-01
影响因子：
15.3
通讯作者：
Rosenberg, S A
中科院分区：
文献类型：
--
作者：
Grimm, E A;Mazumder, A;Zhang, H Z;Rosenberg, S A
在凝集素的白细胞介素2（IL-2）的激活，从癌症患者或正常人的外周血单核白细胞（PBL）的上清液中，导致对21个自然杀伤（NK）抗性的新鲜实体瘤细胞中的20个细胞毒性的表达测试。在10名自体患者的PBL-肿瘤相互作用中，新鲜实体瘤细胞对NK介导的裂解具有抗性，并且来自17名正常个体的新鲜实体瘤细胞对13名同种异体新鲜肿瘤具有抗性。淋巴因子激活的杀伤细胞（LAK）需要在IL-2中培养2-3天才能表达，并且对各种NK抗性的新鲜和培养的肿瘤靶点的溶解活性平行发展。自体IL-2在LAK激活中起作用，以及干扰素去除的IL-2制剂。在IL-2中培养之前照射应答者PBL可防止LAK的发展。LAK前体细胞存在于贴壁细胞耗竭的PBL和NK空胸导管淋巴细胞中，表明前体细胞既不是单核细胞也不是NK细胞。LAK效应细胞表达血清学定义的T细胞标志物OKT.3、Leu-1和4F 2，但不表达单核细胞/NK标志物OKM-1。在85%的患者-新鲜肿瘤组合中，来自癌症患者PBL的LAK对自体新鲜实体瘤进行了溶解。我们的数据提供的证据表明，LAK系统是一种不同于NK或CTL系统的现象，这可能是大量报道的非经典细胞毒性的原因。LAK细胞的生物学作用尚不清楚，尽管有人认为这些细胞可能在对人类实体瘤的免疫监视中起作用。
Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK- resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2 was functional in LAK activation, as well as interferon- depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.