英国伦敦大学Alessio Lanna团队近期取得重要工作进展，他们研究发现端粒的细胞间转移使T细胞免于衰老并促进长期免疫记忆。相关研究成果2022年9月15日在线发表于《自然- 细胞生物学》杂志上。

研究人员发现一些T细胞（主要是幼稚细胞和中央记忆细胞）通过独立于端粒酶作用，从抗原呈递细胞（APC）获取端粒囊泡来延长端粒。 在与这些T细胞接触后，APC降解端粒蛋白复合体以提供端粒，这些端粒被端粒修剪因子TZAP切割，然后转移到免疫突触处的细胞外囊泡中。 端粒囊泡保留了Rad51重组因子，该因子使端粒与T细胞染色体末端融合，平均延长了约3,000个碱基对。 因此，存在抗原特异性T细胞群，其老化命运的决定是基于与APC初始接触后的端粒囊泡转移。 这些获取端粒的T细胞在克隆分裂开始之前就受到保护，不会衰老，从而提供持久的免疫保护。

据介绍，普遍的观点是T淋巴细胞激活端粒酶来延缓衰老。

附：英文原文

Title: An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory

Author: Lanna, Alessio, Vaz, Bruno, DAmbra, Clara, Valvo, Salvatore, Vuotto, Claudia, Chiurchi, Valerio, Devine, Oliver, Sanchez, Massimo, Borsellino, Giovanna, Akbar, Arne N., De Bardi, Marco, Gilroy, Derek W., Dustin, Michael L., Blumer, Brendan, Karin, Michael

Issue&Volume: 2022-09-15

Abstract: The common view is that T lymphocytes activate telomerase to delay senescence. Here we show that some T cells (primarily nave and central memory cells) elongated telomeres by acquiring telomere vesicles from antigen-presenting cells (APCs) independently of telomerase action. Upon contact with these T cells, APCs degraded shelterin to donate telomeres, which were cleaved by the telomere trimming factor TZAP, and then transferred in extracellular vesicles at the immunological synapse. Telomere vesicles retained the Rad51 recombination factor that enabled telomere fusion with T-cell chromosome ends lengthening them by an average of ~3,000 base pairs. Thus, there are antigen-specific populations of T cells whose ageing fate decisions are based on telomere vesicle transfer upon initial contact with APCs. These telomere-acquiring T cells are protected from senescence before clonal division begins, conferring long-lasting immune protection.

DOI: 10.1038/s41556-022-00991-z

Source: https://www.nature.com/articles/s41556-022-00991-z