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

Journal article

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 ~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.

Authors: Lanna, A; Vaz, B; D’Ambra, C; Valvo, S; Vuotto, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature Cell Biology
• Volume: 24
• Pages: 1461-1474
• Publication date: 2022-09-15
• Acceptance date: 2022-08-11
• DOI: 10.1038/s41556-022-00991-z
• EISSN: 1476-4679
• ISSN: 1465-7392
• Language: English
• Keywords: FFR