Mazumder A, Grimm E A, Rosenberg S A
J Immunol. 1983 Feb;130(2):958-64.
Human peripheral blood lymphocytes (PBL), obtained from patients with a variety of malignancies, when incubated in vitro with phytohemagglutinin (PHA), lysed fresh autologous tumors during a short-term 51Cr-release assay. These PHA-activated killer (PAK) cells produced maximum lysis of tumor cells by 4 to 8 hr of co-cultivation. PHA incubation induced the generation of cells lytic for autologous and allogeneic tumors but not autologous or allogeneic PBL. Cold target inhibition studies demonstrated that autologous and allogeneic tumors of various histologic types all shared the determinants recognized by PAK cells. Some adherent cells were necessary for generation of these PAK, but higher numbers were suppressive. Augmentation of tumor cell lysis was seen when adherent cells were partially removed before PHA activation. The PAK effector cell was OKT3+, OKT8+. The precursor cell of the PAK was separated from natural killer (NK) cells on Percoll gradients and was generated from thoracic duct lymphocytes, a population devoid of NK cells. Furthermore, the phenotype of the majority of the precursor cells was OKT3+, OKM1-. Activation by PHA for 2 days was found to be an efficient and convenient method for generating lymphoid cells lytic for fresh autologous human tumor. The biologic and possible therapeutic role of these cells is currently being investigated.
从患有各种恶性肿瘤的患者身上获取的人外周血淋巴细胞(PBL),在体外与植物血凝素(PHA)一起孵育时,在短期51Cr释放试验中能裂解新鲜的自体肿瘤。这些PHA激活的杀伤细胞(PAK)在共培养4至8小时后对肿瘤细胞产生最大程度的裂解。PHA孵育诱导产生对自体和异体肿瘤具有溶解性的细胞,但对自体或异体PBL没有作用。冷靶抑制研究表明,各种组织学类型的自体和异体肿瘤都共享PAK细胞识别的决定簇。产生这些PAK需要一些贴壁细胞,但数量过多则具有抑制作用。在PHA激活前部分去除贴壁细胞时,可观察到肿瘤细胞裂解增强。PAK效应细胞为OKT3 +、OKT8 +。PAK的前体细胞在Percoll梯度上与自然杀伤(NK)细胞分离,并且由胸导管淋巴细胞产生,胸导管淋巴细胞群体中不含NK细胞。此外,大多数前体细胞的表型为OKT3 +、OKM1 -。发现用PHA激活2天是产生对新鲜自体人肿瘤具有溶解性的淋巴细胞的一种有效且便捷的方法。目前正在研究这些细胞的生物学和可能的治疗作用。