SPECIFICITY OF NATURAL CYTOTOXIC REACTIVITY OF NORMAL HUMAN LYMPHOCYTES AGAINST A MYELOID-LEUKEMIA CELL LINE

SPECIFICITY OF NATURAL CYTOTOXIC REACTIVITY OF NORMAL HUMAN LYMPHOCYTES AGAINST A MYELOID-LEUKEMIA CELL LINE
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DOI:
10.1093/jnci/59.1.77
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发表时间:
1977-01-01
影响因子:
10.3
通讯作者:
HERBERMAN, RB
HERBERMAN, RB
中科院分区:
医学1区
文献类型:
--
作者:
ORTALDO, JR;OLDHAM, RK;HERBERMAN, RB

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正常人外周血淋巴细胞对肿瘤培养细胞的天然反应性通过各种细胞毒性试验得到证实。采用4小时细胞毒抑制实验来检测这种自然杀伤的特异性。K-562,一种从慢性骨髓性白血病患者的胸腔积液中提取的悬浮骨髓细胞系,在所有的实验中都被用作靶细胞。新鲜和冷冻的人淋巴细胞作为攻击细胞进行试验。通过将不同数量的未标记(抑制剂)细胞加入淋巴细胞和标记靶细胞的标准混合物(100:1)来竞争性抑制反应性。抑制研究显示了广泛但可重复的特异性模式,大多数但不是所有已建立的人类细胞系测试显着抑制细胞毒性反应。从恶性组织和乳腺癌、肺癌、急性骨髓性和淋巴细胞白血病细胞系中提取的新鲜单细胞悬浮液显示阳性结果。一些已建立的人类细胞系(在与阳性细胞系相同的条件下生长),直接从患者和正常外周血淋巴细胞中获得的冷冻保存的白血病母细胞,对反应性没有抑制或非特异性抑制。阳性结果不仅限于人类细胞:小鼠和大鼠淋巴瘤细胞在体内或培养中传代,但不包括正常小鼠淋巴样细胞或小鼠胎儿组织,可以抑制K-562的细胞毒性。显然,正常人外周血淋巴细胞对K562的细胞毒性是特异性的,并且直接针对存在于许多人已建立的细胞系和一些人和小鼠肿瘤上的抗原。
Natural reactivity of normal human peripheral blood lymphocytes against cultured cells derived from tumors was demonstrated by various cytotoxic assays. A 4-h cytotoxic inhibition assay was used here to examine the specificity of reactivity of this natural killing. K-562, a suspension myeloid cell line derived from the pleural effusion of a patient with chronic myelogenous leukemia, was used as the target cell in all assays. Fresh and frozen human lymphocytes were tested as attacker cells. Competitive inhibition of the reactivity was performed by the addition of varying numbers of unlabeled (inhibitor) cells to a standard mixture of lymphocytes and labeled target cells (100:1). The inhibition studies demonstrated a broad but reproducible pattern of specificity, with most but not all established human cell lines tested significantly inhibiting the cytotoxic reaction. Fresh single cell suspensions from malignant tissues and cell lines derived from carcinomas of the breast and lung and from acute myelogenous and lymphoblastic leukemias gave positive results. Some established human cell lines (grown under the same conditions as the positive lines), cryopreserved leukemia blast cells obtained directly from patients and normal peripheral blood lymphocytes caused either no inhibition or nonspecific inhibition of reactivity. Positive results were not limited to human cells: mouse and rat lymphoma cells passaged in vivo or in culture, but not normal murine lymphoid cells or mouse fetal tissue, could inhibit the cytotoxicity against K-562. Apparently the cytotoxicity of normal human peripheral blood lymphocytes against K562 is specific and is directed against antigen(s) present on many human established cell lines and on some human and murine tumors.