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Aging-related changes in human T-cell repertoire over 20years delineated by deep sequencing of peripheral T-cell receptors.

Abstract：

:Recent deep sequencing studies on T-cell receptor (TCR) repertoire have provided robust data to characterize diversity of T-cell immune responsiveness to a wide variety of peptide antigens, including viral and tumor antigens. The human TCR repertoire declines with age, but this decline has not been fully investigated longitudinally in individuals. Using a deep sequencing approach, we analyzed TCRβ repertoires longitudinally over approximately 20years, with ages ranging from 23 to 50years at the start (23 to 65years overall), in peripheral-blood CD4 and CD8 T-cell populations that were collected and cryopreserved 3 times at intervals of approximately 10years from each of 6 healthy adults (3 men and 3 women). Sequence data at the hypervariable complementarity determining region 3 (CDR3) in the TCRB gene locus were evaluated by applying a random-coefficient statistical regression model. Two outcomes were analyzed: total number of distinct TCRB CDR3 sequences as a TCR diversity metric, and clonality of the T-cell populations. TCR repertoire diversity decreased (p<0.001) and frequencies of clonal populations increased (p=0.003) with age in CD8 T cells, whereas CD4 T cells retained fairly diverse TCR repertoires along with relatively low clonality. We also found that approximately 10-30% and 30-80% of read sequences in CD4 and CD8 T cells, respectively, overlapped at different ages within each individual, indicating long-term stable maintenance of T-cell clonal composition. Moreover, many of the most frequent TCRB CDR3 sequences (i.e., top T-cell clones) persisted over 20years, and some of them expanded and exerted a dominating influence on clonality of peripheral T-cell populations. It is thus possible that persistence or expansion of top T-cell clones is a driver of T-cell immunity aging, and therefore represents a potential interventional target.

journal_name

Exp Gerontol

journal_title

Experimental gerontology

authors

Yoshida K,Cologne JB,Cordova K,Misumi M,Yamaoka M,Kyoizumi S,Hayashi T,Robins H,Kusunoki Y

doi

10.1016/j.exger.2017.05.015

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

29-37

eissn

0531-5565

issn

1873-6815

pii

S0531-5565(17)30272-3

journal_volume

pub_type

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Aging-related changes in human T-cell repertoire over 20years delineated by deep sequencing of peripheral T-cell receptors.