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

• Published in: Experimental gerontology 2017-10, Vol.96, p.29-37
• Main Authors: Yoshida, Kengo, Cologne, John B., Cordova, Kismet, Misumi, Munechika, Yamaoka, Mika, Kyoizumi, Seishi, Hayashi, Tomonori, Robins, Harlan, Kusunoki, Yoichiro
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aging - immunology; CD4-Positive T-Lymphocytes - physiology; CD8-Positive T-Lymphocytes - physiology; Clone Cells - physiology; Female; Humans; Male; Middle Aged; Receptors, Antigen, T-Cell - physiology; Sex Characteristics; T-Lymphocyte Subsets - physiology; Young Adult
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2017.05.015

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