Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells.
Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells.
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DOI：
10.1084/jem.157.3.884
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发表时间：
1983-03-01
期刊：
影响因子：
--
通讯作者：
Rosenberg SA
中科院分区：
文献类型：
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作者：
Grimm EA;Ramsey KM;Mazumder A;Wilson DJ;Djeu JY;Rosenberg SA
人外周血淋巴细胞（PBL）在部分纯化的和无凝集素的白细胞介素2中培养导致产生具有裂解自然杀伤（NK）抗性的新鲜人肿瘤细胞的独特性质的细胞毒性效应细胞。我们将这些效应细胞称为“淋巴因子激活的杀伤”细胞（LAK）。LAK由正常和癌症患者的PBL产生，并且能够溶解来自所有测试的组织学肿瘤类型的自体和同种异体肿瘤细胞。我们以前的研究表明，LAK现象是不同的细胞毒性胸腺衍生淋巴细胞（CTL）或NK系统的基础上的各种标准。这项研究报告说，涉及的细胞类型也是不同的，由表型特征确定。LAK效应细胞表型与同种免疫CTL平行分析，发现LAK对单克隆抗T细胞抗体OKT-3或OKT-8加补体同样敏感。相反，LAK前体对OKT-3或Leu-1抗体加补体不敏感，而当使用相同的PBL应答者群体进行测试时，产生同种免疫CTL的能力完全消失;事实上，发现LAK的产生增加了五到六倍，清楚地表明LAK前体细胞不是由这些抗体定义的T淋巴细胞。发现LAK前体在NK细胞富集的Percoll梯度级分中是丰富的，其已经耗尽了29 ° C E玫瑰花结“高亲和力”T细胞。然而，发现LAK前体细胞与大多数NK细胞不同，因为用单克隆抗体OKM-1、Leu-7或OKT-11裂解新鲜PBL显著耗尽或完全消除NK活性，而随后激活剩余细胞产生高水平的LAK，并且在某些情况下增加LAK水平。LAK前体细胞除分布于PBL外，还分布于胸腺、骨髓、脾脏、淋巴结和胸导管。因此，虽然负责LAK活性的活化和表达的细胞与经典的T细胞介导的CTL和NK细胞系统具有一些共同的特征，但是LAK前体细胞是明显不同的，如通过使用单克隆抗体和补体的表型分析所确定的，并且目前必须被分类为“空”细胞。
Culture of human peripheral blood lymphocytes (PBL) in partially purified and lectin-free interleukin 2 results in the generation of cytotoxic effector cells which have the unique property of lysing natural killer (NK)-resistant fresh human tumor cells. We have termed these effector cells “lymphokine- activated killer” cells (LAK). LAK are generated from both normal and cancer patients' PBL and are able to lyse both autologous and allogeneic tumor cells from all histologic tumor types tested. Our previous studies suggested that the LAK phenomenon was distinct from either the cytotoxic thymus-derived lymphocyte (CTL) or NK systems based on a variety of criteria. This study reports that the cell type involved is also distinct, as determined by phenotypic characteristics. The LAK effector cell phenotype was analyzed in parallel with alloimmune CTL, and LAK were found to be similarly susceptible to the monoclonal anti-T cell antibodies OKT-3 or OKT-8 plus complement. In contrast the LAK precursor was not susceptible to the OKT-3 or Leu-1 antibodies plus complement, while the ability to generate alloimmune CTL was totally obliterated when tested using the same PBL responder population; in fact, generation of LAK was found to be augmented five- to sixfold, clearly suggesting that LAK precursor cells are not T lymphocytes as defined by these antibodies. LAK precursors were found to be abundant in NK cell-enriched Percoll gradient fractions, which had been depleted of the 29 degrees C E- rosetting “high affinity” T cells. However, LAK precursors were found to be distinct from the majority of NK cells since lysis of fresh PBL with the monoclonal antibodies OKM-1, Leu-7, or OKT-11 significantly depleted or totally eliminated NK activity, while subsequent activation of the remaining cells generated high levels of LAK and in some cases augmented levels of LAK. LAK precursors were found to be distributed in the thymus, bone marrow, spleen, lymph node, and thoracic duct in addition to the PBL. Therefore, while the cell(s) responsible for activation and expression of LAK activity have some common features with the classic T cell-mediated CTL and NK cell systems, the LAK precursor cells are clearly distinct as determined by phenotype analysis using monoclonal antibodies and complement, and at present must be classified as a “null” cell.