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T cell immunity does not age in a long-lived rodent species

Authors :
Imad Shams
Mikhail Shugay
Ekaterina A. Bogdanova
Dmitriy A Miskevich
Mark Izraelson
Alexey N. Davydov
Sergey A. Lukyanov
Dmitriy A. Bolotin
Ilgar Z. Mamedov
Olga V. Britanova
Lyliya N Barbashova
Maria Dronina
Dmitriy M. Chudakov
Dmitriy B. Staroverov
Tatiana O Nakonechnaya
Ekaterina Y Kondratyuk
Publication Year :
2018
Publisher :
Cold Spring Harbor Laboratory, 2018.

Abstract

Numerous studies have demonstrated that the percentage of naïve T cells and diversity of T cell receptor (TCR) repertoire decrease with age, with some findings likewise suggesting that increased repertoire diversity may be associated with longer lifespan and healthy aging. In this work, we have analyzed peripheral TCR diversity from humans, mice, and blind mole-rats (Spalax spp.)—long-lived, hypoxia- and cancer-tolerant rodents. We employed a quantitative approach to TCR repertoire profiling based on 5’RACE with unique molecular identifiers (UMI) to achieve accurate comparison of repertoire diversity, which also required development of specific wet lab protocol and TCR gene reference for Spalax. Our direct comparison reveals a striking phenomenon. Whereas TCR diversity of mice and humans decreases with age, resulting primarily from the shrinkage of the naive T cell pool, Spalax TCR diversity remains stable even for the animals that reach extreme old age (15-17 years). This indicates that T cell immunity does not meaningfully age in long-lived rodents, at least in terms of the classical understanding of immunosenescence, which is associated with the accumulation of large numbers of memory clones. We suggest that the extraordinary longevity of Spalax may be attributable at least in part to the distinctive organization of their T cell immunity. Our findings should therefore encourage a close re-examination of the contribution of immunosenescence to life span in mammals.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....d0527eb90dbce99a7b0a9987bea7f6b5
Full Text :
https://doi.org/10.1101/259374