INSERM, Centre de Physiopathologie de Toulouse Purpan, Section Dynamique moléculaire des interactions lymphocytaires, Toulouse, France.
J Cell Mol Med. 2009 Sep;13(9B):3834-46. doi: 10.1111/j.1582-4934.2008.00586.x. Epub 2008 Oct 6.
It is well established that cytotoxic T lymphocytes (CTL) can kill target cells offering a very small number of specific peptide/MHC complexes (pMHC). It is also known that lethal hit delivery is a very rapid response that occurs within a few minutes after cell-cell contact. Whether cytotoxicity is efficient and rapid in the context of CTL interaction with target cells derived from solid tumours is still elusive. We addressed this question by visualizing the dynamics of human CTL interaction with melanoma cells and their efficiency in eliciting cytotoxicity. Our results show that in spite of CTL activation to lethal hit delivery, killing of melanoma cells is not efficient. Time-lapse microscopy experiments demonstrate that individual CTL rapidly polarize their lytic machinery towards target cells, yet the apoptotic process in melanoma cells is defective or 'delayed' as compared to conventional targets. These results indicate that although CTL activation to lethal hit delivery can be viewed as a 'digital' phenomenon rapidly triggered by a few ligands, melanoma cell annihilation is an 'analogue' response requiring multiple hits and prolonged contact time.
已证实细胞毒性 T 淋巴细胞 (CTL) 可以杀死提供极少数特定肽/主要组织相容性复合体 (pMHC) 的靶细胞。人们还知道，致死性打击的传递是一种非常迅速的反应，在细胞-细胞接触后的几分钟内发生。CTL 与源自实体瘤的靶细胞相互作用时，细胞毒性是否高效和迅速仍然难以捉摸。我们通过可视化人 CTL 与黑色素瘤细胞的相互作用及其引发细胞毒性的效率来解决这个问题。我们的结果表明，尽管 CTL 被激活以进行致死性打击传递，但黑色素瘤细胞的杀伤效率并不高。延时显微镜实验表明，单个 CTL 会迅速将其溶细胞机制向靶细胞极化，然而与传统靶细胞相比，黑色素瘤细胞中的凋亡过程是有缺陷的或“延迟的”。这些结果表明，尽管 CTL 被激活以进行致死性打击传递可以被视为一种由少数配体快速触发的“数字”现象，但黑色素瘤细胞的消除是一种需要多次打击和延长接触时间的“模拟”反应。
