An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory.
An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory.
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DOI：
10.1038/s41556-022-00991-z
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发表时间：
2022-10
影响因子：
21.3
通讯作者：
Karin M
中科院分区：
文献类型：
--
作者：
Lanna A;Vaz B;D'Ambra C;Valvo S;Vuotto C;Chiurchiù V;Devine O;Sanchez M;Borsellino G;Akbar AN;De Bardi M;Gilroy DW;Dustin ML;Blumer B;Karin M
普遍的观点认为，T淋巴细胞激活端粒酶来延缓衰老。在这里，我们表明，一些T细胞（主要是幼稚和中央记忆细胞）通过从抗原呈递细胞（APC）获得端粒囊泡独立于端粒酶作用延长端粒。在与这些T细胞接触时，APC降解shelterin以捐赠端粒，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，平均延长约3000个碱基对。因此，存在抗原特异性T细胞群体，其衰老命运决定基于与APC初始接触后的端粒囊泡转移。这些获得端粒的T细胞在克隆分裂开始之前被保护免于衰老，从而赋予持久的免疫保护。
The common view is that T-lymphocytes activate telomerase to delay senescence. Here we show that some T cells (primarily naïve 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 ~3000 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 begin, conferring long-lasting immune protection.
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影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
17.1
作者：
Boraschi, Diana;Aguado, M. Teresa;Del Giudice, Giuseppe
通讯作者：
Del Giudice, Giuseppe
影响因子：
12.4
作者：
Dustin ML;Groves JT
通讯作者：
Groves JT
影响因子：
3.1
作者：
Huet, Olivier;Ramsey, Debbie;Chin-Dusting, Jaye P. F.
通讯作者：
Chin-Dusting, Jaye P. F.