Intercellular telomere transfer extends T cell lifespan

Vaz, B.; Vuotto, C.; Valvo, S.; D'Ambra, C.; Esposito, F. M.; Chiurchiu, V.; Devine, O.; Sanchez, M.; Borsellino, G.; Gilroy, D.; Akbar, A.; Dustin, M.; Karin, M.; Lanna, A.

doi:10.1101/2020.10.09.331918

bioRxiv · 10.1101/2020.10.09.331918

Intercellular telomere transfer extends T cell lifespan

Vaz, B.·Vuotto, C.·Valvo, S.·D'Ambra, C.·Esposito, F. M.·Chiurchiu, V.·Devine, O.·Sanchez, M.·Borsellino, G.·Gilroy, D.·Akbar, A.·Dustin, M.·Karin, M.·Lanna, A.

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Abstract

The common view is that T-lymphocytes activate telomerase, a DNA polymerase that extends telomeres at chromosome ends, to delay senescence. We show that independently of telomerase, T cells elongate telomeres by acquiring telomere vesicles from antigen-presenting cells (APCs). Upon contact with T cells, APCs degraded shelterin to donate telomeres, which were cleaved by TZAP, and then transferred in extracellular vesicles (EVs) at the immunological synapse. Telomere vesicles retained the Rad51 recombination factor that enabled them to fuse with T cell chromosomal ends causing an average lengthening of [~]3000 base pairs. Thus, we identify a previously unknown telomere transfer program that supports T cell lifespan.

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Vaz, B., Vuotto, C., Valvo, S., D'Ambra, C., Esposito, F. M., Chiurchiu, V., Devine, O., Sanchez, M., Borsellino, G., Gilroy, D., Akbar, A., Dustin, M., Karin, M., Lanna, A.. 2020-10-09. Intercellular telomere transfer extends T cell lifespan. https://doi.org/10.1101/2020.10.09.331918

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