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Telomere vesicle transfer protects T cells from senescence

Nature Aging volume 2, page 872 (2022)Cite this article

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In a recent study published in Nature Cell Biology, Lanna and colleagues showed that a subpopulation of T cells (primarily naive and central memory cells) elongated their telomeres by acquiring telomere vesicles from APCs following immune synapse formation stimulated by an antigen pool (Epstein–Barr virus, influenza and cytomegalovirus lysates). This effect was independent of telomerase activity, as T cells deficient in telomerase (TERT-knockout generated by CRISPR–Cas9 transfection) still showed elongated telomeres after exposure to APCs and the antigen pool. Looking for mechanisms, the authors demonstrated that, upon contact with T cells, the APCs degraded the telomere-protecting complex shelterin to donate their telomeres. Telomeres were subsequently cleaved by the trimming factor TZAP and transferred to T cells via extracellular vesicles at the immunological synapse. Immunofluorescence analysis revealed that telomere vesicles retained the RAD51 recombination factor that enabled telomere fusion with T cell chromosome ends, lengthening them by an average of about 3,000 base pairs. Telomere vesicles retaining RAD51 extended the longevity of T cells, and their transfer reinforced long-term immunological memory against influenza in mice.

Together, the results identify the acquisition of telomere from APCs through extracellular vesicles as a mechanism used by a subpopulation of antigen-specific T cells to protect themselves from senescence before clonal division begins, conferring long-lasting immune protection. Telomere shortening is a feature of advanced aging that leads to accumulation of senescent T cells, and, unlike T cells with APC telomeres, these cells have an impaired ability to undergo antigen-specific expansion. Thus, the findings from this work may inspire new ways to address immunosenescence in the context of aging.

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Change history

  • 26 October 2022

    In the version of this article initially published, Alessio Lanna was not cited as the first author of the study discussed, which has now been amended in the HTML and PDF versions of the article.

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  1. Nature Aging https://www.nature.com/nataging

    Yahyah Aman

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  1. Yahyah Aman
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Correspondence to Yahyah Aman.

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Aman, Y. Telomere vesicle transfer protects T cells from senescence. Nat Aging 2, 872 (2022). https://doi.org/10.1038/s43587-022-00296-8

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