Karas M, Zaks T Z, Liu J L, LeRoith D
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-1770, USA.
Mol Biol Cell. 1999 Dec;10(12):4441-50. doi: 10.1091/mbc.10.12.4441.
Previous studies have found conflicting associations between susceptibility to activation-induced cell death and the cell cycle in T cells. However, most of the studies used potentially toxic pharmacological agents for cell cycle synchronization. A panel of human melanoma tumor-reactive T cell lines, a CD8+ HER-2/neu-reactive T cell clone, and the leukemic T cell line Jurkat were separated by centrifugal elutriation. Fractions enriched for the G0-G1, S, and G2-M phases of the cell cycle were assayed for T cell receptor-mediated activation as measured by intracellular Ca(2+) flux, cytolytic recognition of tumor targets, and induction of Fas ligand mRNA. Susceptibility to apoptosis induced by recombinant Fas ligand and activation-induced cell death were also studied. None of the parameters studied was specific to a certain phase of the cell cycle, leading us to conclude that in nontransformed human T cells, both activation and apoptosis through T cell receptor activation can occur in all phases of the cell cycle.
以往研究发现，T细胞中激活诱导的细胞死亡易感性与细胞周期之间的关联存在矛盾。然而，大多数研究使用了具有潜在毒性的药理试剂来进行细胞周期同步化。通过离心淘析法分离了一组人黑色素瘤肿瘤反应性T细胞系、一个CD8 + HER-2/neu反应性T细胞克隆以及白血病T细胞系Jurkat。对富含细胞周期G0-G1、S和G2-M期的组分进行检测，以测量细胞内Ca(2+)通量、肿瘤靶标的溶细胞识别以及Fas配体mRNA的诱导，从而评估T细胞受体介导的激活。还研究了重组Fas配体诱导的凋亡易感性和激活诱导的细胞死亡。所研究的参数均不特定于细胞周期的某一阶段，这使我们得出结论，在未转化的人T细胞中，通过T细胞受体激活引发的激活和凋亡可发生于细胞周期的所有阶段。
