Vollenweider I, Moser R, Groscurth P
Division of Cell Biology, University of Zürich-Irchel, Switzerland.
Cancer Immunol Immunother. 1994 Nov;39(5):305-12. doi: 10.1007/BF01519983.
A series of 62 lymphokine-activated killer cell (LAK) cultures from 44 different donors was investigated for the distribution of various CD markers during a cultivation period of 3 weeks. Great differences in the phenotypic pattern were found between different donors, but similar changes of the subset pattern of various donors allowed a classification of the LAK cultures into four distinct LAK types. LAK type 1 was characterised by low numbers of CD3+ cells and high values for CD56+ cells. In LAK type 2 cultures gamma/delta TCR+ cells extensively proliferated, whereas in LAK type 3 cultures the CD57 and CD8 values increased considerably. LAK type 4 cultures did not show any of these characteristics. The resulting phenotype of a LAK culture was donor-specific, as LAK cultures established from the same peripheral blood mononuclear cells (PBMC), fresh or after cryopreservation, or from PBMC obtained from the same donor at different venous punctures, always developed the same phenotype. A clear correlation between phenotype and killing activity could only be found for LAK type 1 cultures, which always developed high lytic activity. Long-term IL-2 stimulation induced high levels of perforin-positive cells in LAK cultures but the perforin content did not correlate with the cytotoxicity. The transcription pattern for various cytokines only varied slightly between the cultures. Messenger RNA for granulocyte/macrophage- colony-stimulating factor, interferon gamma, tumour necrosis factor alpha, interleukin-4 (IL-4) and IL-5 were found in almost all cultures during the entire cultivation period, whereas mRNA for IL-2 was never detected. Most variations in the transcription pattern were observed for IL-6 and IL-7. However, no correlation could be found between the endogenous cytokine production and the phenotype or lytic activity of the LAK cultures. Further studies are required to determine the factors that cause lymphocyte subsets from a specific donor to proliferate preferentially under long-term IL-2 stimulation.
对来自44个不同供体的62份淋巴因子激活的杀伤细胞（LAK）培养物进行了研究，观察其在3周培养期内各种CD标志物的分布情况。不同供体之间的表型模式存在很大差异，但不同供体亚群模式的相似变化使得LAK培养物可分为四种不同的LAK类型。LAK-1型的特征是CD3 +细胞数量少，CD56 +细胞值高。在LAK-2型培养物中，γ/δTCR +细胞大量增殖，而在LAK-3型培养物中，CD57和CD8值显著增加。LAK-4型培养物未表现出这些特征中的任何一种。LAK培养物的最终表型是供体特异性的，因为从相同的外周血单个核细胞（PBMC）（新鲜的或冷冻保存后），或从同一供体在不同静脉穿刺获得的PBMC建立的LAK培养物，总是呈现相同的表型。仅在LAK-1型培养物中发现表型与杀伤活性之间存在明显相关性，LAK-1型培养物总是具有高裂解活性。长期IL-2刺激在LAK培养物中诱导出高水平的穿孔素阳性细胞，但穿孔素含量与细胞毒性无关。不同培养物之间各种细胞因子的转录模式仅略有不同。在整个培养期内，几乎所有培养物中都发现了粒细胞/巨噬细胞集落刺激因子、干扰素γ、肿瘤坏死因子α、白细胞介素-4（IL-4）和IL-5的信使RNA，而从未检测到IL-2的mRNA。IL-6和IL-7的转录模式变化最大。然而，在LAK培养物的内源性细胞因子产生与表型或裂解活性之间未发现相关性。需要进一步研究以确定在长期IL-2刺激下导致特定供体的淋巴细胞亚群优先增殖的因素。
