Chan Weng-Chee, Linn Yeh-Ching
School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
Department of Haematology, Singapore General Hospital, Academia, Level 3, 20, College Road, Singapore, 169856, Singapore.
Cytotechnology. 2016 Aug;68(4):735-48. doi: 10.1007/s10616-014-9825-x. Epub 2014 Dec 7.
Cytokine-induced killer (CIK) cells and T cells expanded by co-stimulation with beads presenting anti-CD3 and -CD28 antibodies are both polyclonal T cells under intensive laboratory and clinical studies, but there has not been any direct comparison between both. We compared the expansion, memory T cell subsets and cytotoxicity for T cells expanded in parallel by the two methods. Bead-stimulated T cells showed superior expansion as compared to CIK cells on D14 of culture. Bead-stimulated T cells consisted of a significantly higher CD4(+) subset and significantly lower CD8(+) subset as compared to CIK cells, as well as a higher proportion of less terminally differentiated T cells and a higher proportion of homing molecules. On the other hand, CIK cells exhibited significantly superior cytotoxicity against two myelomonocytic leukemia cell lines (THP-1 and U937) and two RCC cell lines (786.0 and CaKi-2). The cytotoxicity on D14 against THP-1 was 58.1 % for CIK cells and 8.3 % for bead-stimulated T cells at E:T of 10:1 (p < 0.01). Cytotoxicity correlated positively with the proportion of the CD8 subset in the culture and was independent of NKG2D recognition of susceptible targets. Polyclonal T cells expanded by different methods exhibit different characteristics which may define the specific role of each in different clinical scenario. We postulate that the more potent CIK cells may offer short term benefit while bead-stimulated T cells may offer a more sustained immune response.
细胞因子诱导的杀伤细胞(CIK)和通过与呈递抗CD3和抗CD28抗体的珠子共刺激而扩增的T细胞,在深入的实验室和临床研究中均为多克隆T细胞,但两者之间尚未进行任何直接比较。我们比较了通过这两种方法平行扩增的T细胞的扩增情况、记忆性T细胞亚群和细胞毒性。与CIK细胞相比,在培养第14天时,珠子刺激的T细胞显示出更好的扩增效果。与CIK细胞相比,珠子刺激的T细胞由比例显著更高的CD4(+)亚群和比例显著更低的CD8(+)亚群组成,以及比例更高的终末分化程度较低的T细胞和比例更高的归巢分子。另一方面,CIK细胞对两种髓单核细胞白血病细胞系(THP-1和U937)和两种肾细胞癌细胞系(786.0和CaKi-2)表现出显著更强的细胞毒性。在效应细胞与靶细胞比例为10:1时,CIK细胞在第14天对THP-1的细胞毒性为58.1%,珠子刺激的T细胞为8.3%(p < 0.01)。细胞毒性与培养物中CD8亚群的比例呈正相关,且与易感靶标的NKG2D识别无关。通过不同方法扩增的多克隆T细胞表现出不同特征,这可能决定了它们在不同临床场景中的特定作用。我们推测,更强效的CIK细胞可能提供短期益处,而珠子刺激的T细胞可能提供更持久的免疫反应。