Jemma C, Cignetti A, Geuna M, Caretto P, Vai S, Forni G
Institute of Microbiology, University of Turin, Italy.
J Immunother (1991). 1991 Jun;10(3):189-99. doi: 10.1097/00002371-199106000-00005.
The effectiveness of "standard" lymphokine-activated killer (LAK) cells, recovered after 6 days, and of "standard" adherent LAK (A-LAK) cells, recovered after 14 days of culture in the presence of recombinant interleukin-2 (rIL-2) from peripheral blood lymphocytes of 21 healthy donors, was assessed through comparison of their proliferation, surface markers, cytotoxic activity, lymphokine production, and antitumor activity. In the presence of rIL-2, plastic adherent precursors of A-LAK cells proliferated much better than those of "standard LAK" cells and expanded even more than 300-fold. However, the final cell recovery of A-LAK was always lower because of their very few precursors, and the total lytic units (LUs) generated in A-LAK cultures were always lower for the same reason. On the other hand, the lytic activity of each A-LAK cell was always higher than that of a LAK cell. This was particularly evident on day 6 of culture. Removal of nonadherent cells after the first 24 h culture resulted in a significant enrichment in CD3-CD56+ and CD8+CD56+ cells in A-LAK cells, with a marginal number of CD4+ cells. A significant direct correlation between LUs and A-LAK CD3-CD56+ percentage was found. In the presence of rIL-2, A-LAK cells produced higher amounts of tumor necrosis factor-alpha and interferon-gamma than LAK cells, while only A-LAK cells produced IL-1 beta and small amounts of IL-4. Neither LAK nor A-LAK produced IL-2. In the absence of injections of IL-2, LAK and A-LAK cells were equally able to inhibit the growth of a human T-cell lymphoma in immunosuppressed nude mice.
对从21名健康供体的外周血淋巴细胞中分离得到的“标准”淋巴因子激活的杀伤细胞(LAK细胞,培养6天后收获)以及在重组白细胞介素-2(rIL-2)存在下培养14天后收获的“标准”贴壁LAK细胞(A-LAK细胞)的有效性,通过比较它们的增殖、表面标志物、细胞毒性活性、淋巴因子产生及抗肿瘤活性进行了评估。在rIL-2存在的情况下,A-LAK细胞的塑料贴壁前体细胞比“标准LAK”细胞的前体细胞增殖得更好,甚至扩增超过300倍。然而,由于A-LAK细胞的前体细胞非常少,其最终细胞收获量总是较低,并且由于同样的原因,A-LAK培养物中产生的总裂解单位(LU)也总是较低。另一方面,每个A-LAK细胞的裂解活性总是高于LAK细胞。这在培养第6天时尤为明显。在最初24小时培养后去除非贴壁细胞,导致A-LAK细胞中CD3-CD56+和CD8+CD56+细胞显著富集,而CD4+细胞数量很少。发现LU与A-LAK细胞CD3-CD56+百分比之间存在显著的直接相关性。在rIL-2存在的情况下,A-LAK细胞产生的肿瘤坏死因子-α和干扰素-γ比LAK细胞多,而只有A-LAK细胞产生IL-1β和少量IL-4。LAK细胞和A-LAK细胞均不产生IL-2。在不注射IL-2的情况下,LAK细胞和A-LAK细胞在免疫抑制的裸鼠中同样能够抑制人T细胞淋巴瘤的生长。