Department of Applied Physics, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Nat Commun. 2023 Sep 27;14(1):6035. doi: 10.1038/s41467-023-41634-7.
γδ T cells play a pivotal role in protection against various types of infections and tumours, from early childhood on and throughout life. They consist of several subsets characterised by adaptive and innate-like functions, with Vγ9Vδ2 being the largest subset in human peripheral blood. Although these cells show signs of cytotoxicity, their modus operandi remains poorly understood. Here we explore, using live single-cell imaging, the cytotoxic functions of γδ T cells upon interactions with tumour target cells with high temporal and spatial resolution. While γδ T cell killing is dominated by degranulation, the availability of lytic molecules appears tightly regulated in time and space. In particular, the limited co-occurrence of granzyme B and perforin restrains serial killing of tumour cells by γδ T cells. Thus, our data provide new insights into the cytotoxic arsenal and functions of γδ T cells, which may guide the development of more efficient γδ T cell based adoptive immunotherapies.
γδ T 细胞在抵御各种类型的感染和肿瘤方面发挥着关键作用，从婴幼儿时期到整个生命周期都发挥着作用。它们由几个亚群组成，具有适应性和先天样功能，其中 Vγ9Vδ2 是人类外周血中最大的亚群。尽管这些细胞表现出细胞毒性的迹象，但它们的作用机制仍知之甚少。在这里，我们使用活细胞单细胞成像技术，以高时间和空间分辨率探索 γδ T 细胞与肿瘤靶细胞相互作用时的细胞毒性功能。虽然 γδ T 细胞的杀伤作用主要由脱颗粒作用主导，但溶细胞分子的可用性似乎在时间和空间上受到严格调控。特别是，颗粒酶 B 和穿孔素的有限共表达限制了 γδ T 细胞对肿瘤细胞的连续杀伤。因此，我们的数据为 γδ T 细胞的细胞毒性武器库和功能提供了新的见解，这可能为更有效的基于 γδ T 细胞的过继免疫疗法的发展提供指导。
