Flomenberg N, Welte K, Mertelsmann R, O'Reilly R, Dupont B
J Immunol. 1983 Jun;130(6):2635-43.
Bulk cultured cell lines with natural killer (NK) activity were derived by in vitro culture with interleukin 2-containing conditioned medium (IL 2-CM) of peripheral blood mononuclear leukocytes (PBL) from patients with primary T cell deficiencies. Lines were developed from three patients with severe combined immunodeficiency (SCID) and one patient with Nezelof's syndrome and contained several populations of cells with distinct phenotypes. All lines contained a cell population expressing the Leu-5 (50K) (sheep red blood cell receptor), 3A1 (40K), and OKT10 antigens, but lacking the pan T cell antigens Leu-1 (67K) and Leu-4 (19K) as well as the markers of T cell subsets Leu-2a (32K) and Leu-3a (56K). These cells failed to express the Leu-7 antigen and only weakly expressed OKM1. In addition, one line contained a population of Leu-5+, 3A1+, OKT10+, Leu-2a+, Leu 1-, and Leu 4- cells. Three of the lines also contained populations with classic T cell (Leu-1 and-Leu 4+) phenotypes. The lines were enriched in NK activity compared with the PBL from which they were derived. Their growth was strictly dependent on IL 2-CM. Highly purified IL 2, lacking any other detectable protein contaminants or lymphokine activities, was capable of supporting the growth of the Leu-5+, 3A1+ "null" cell populations from these lines without alteration in their functional activity or phenotype. Thus, studies of in vitro expanded cell lines from patients with severe disorders of T cell function and thymic involution indicate that this "null" cell population does not require thymic maturation to develop its effector function. This "null" cell population can be maintained in vitro in the presence of IL 2. This finding is analogous to the data obtained from study of NK cells in athymic (nude) mice.
通过用来自原发性T细胞缺陷患者的外周血单个核白细胞(PBL)的含白细胞介素2的条件培养基(IL-2-CM)进行体外培养,获得了具有自然杀伤(NK)活性的大量培养细胞系。这些细胞系来自3例严重联合免疫缺陷(SCID)患者和1例内泽洛夫综合征患者,包含几个具有不同表型的细胞群体。所有细胞系都含有一个表达Leu-5(50K)(绵羊红细胞受体)、3A1(40K)和OKT10抗原,但缺乏泛T细胞抗原Leu-1(67K)和Leu-4(19K)以及T细胞亚群标志物Leu-2a(32K)和Leu-3a(56K)的细胞群体。这些细胞不表达Leu-7抗原,仅微弱表达OKM1。此外,一个细胞系含有一群Leu-5 +、3A1 +、OKT10 +、Leu-2a +、Leu 1 -和Leu 4 -细胞。其中3个细胞系还含有具有经典T细胞(Leu-1和-Leu 4 +)表型的细胞群体。与产生它们的PBL相比,这些细胞系的NK活性增强。它们的生长严格依赖于IL-2-CM。高度纯化的IL-2,缺乏任何其他可检测到的蛋白质污染物或淋巴因子活性,能够支持这些细胞系中Leu-5 +、3A1 +“裸”细胞群体的生长,而不会改变其功能活性或表型。因此,对T细胞功能严重紊乱和胸腺退化患者的体外扩增细胞系的研究表明,这种“裸”细胞群体在发育其效应功能时不需要胸腺成熟。这种“裸”细胞群体在IL-2存在下可在体外维持。这一发现与从无胸腺(裸)小鼠的NK细胞研究中获得的数据相似。