Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets
A diverse T cell receptor (TCR) repertoire is essential for protection against a variety of pathogens, and TCR repertoire size is believed to decline with age. However, the precise size of human TCR repertoires, in both total and subsets of T cells, as well as their changes with age, are not fully c...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2022-09-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI158122 |
| _version_ | 1797634616053465088 |
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| author | Xiaoping Sun Thomas Nguyen Achouak Achour Annette Ko Jeffrey Cifello Chen Ling Jay Sharma Toyoko Hiroi Yongqing Zhang Chee W. Chia William Wood III Wells W. Wu Linda Zukley Je-Nie Phue Kevin G. Becker Rong-Fong Shen Luigi Ferrucci Nan-ping Weng |
| author_facet | Xiaoping Sun Thomas Nguyen Achouak Achour Annette Ko Jeffrey Cifello Chen Ling Jay Sharma Toyoko Hiroi Yongqing Zhang Chee W. Chia William Wood III Wells W. Wu Linda Zukley Je-Nie Phue Kevin G. Becker Rong-Fong Shen Luigi Ferrucci Nan-ping Weng |
| author_sort | Xiaoping Sun |
| collection | DOAJ |
| description | A diverse T cell receptor (TCR) repertoire is essential for protection against a variety of pathogens, and TCR repertoire size is believed to decline with age. However, the precise size of human TCR repertoires, in both total and subsets of T cells, as well as their changes with age, are not fully characterized. We conducted a longitudinal analysis of the human blood TCRα and TCRβ repertoire of CD4+ and CD8+ T cell subsets using a unique molecular identifier–based (UMI-based) RNA-seq method. Thorough analysis of 1.9 × 108 T cells yielded the lower estimate of TCR repertoire richness in an adult at 3.8 × 108. Alterations of the TCR repertoire with age were observed in all 4 subsets of T cells. The greatest reduction was observed in naive CD8+ T cells, while the greatest clonal expansion was in memory CD8+ T cells, and the highest increased retention of TCR sequences was in memory CD8+ T cells. Our results demonstrated that age-related TCR repertoire attrition is subset specific and more profound for CD8+ than CD4+ T cells, suggesting that aging has a more profound effect on cytotoxic as opposed to helper T cell functions. This may explain the increased susceptibility of older adults to novel infections. |
| first_indexed | 2024-03-11T12:10:04Z |
| format | Article |
| id | doaj.art-be9e3fbb629f4693b28c5ccd2679bf6e |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:10:04Z |
| publishDate | 2022-09-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-be9e3fbb629f4693b28c5ccd2679bf6e2023-11-07T16:19:17ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-09-0113217Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsetsXiaoping SunThomas NguyenAchouak AchourAnnette KoJeffrey CifelloChen LingJay SharmaToyoko HiroiYongqing ZhangChee W. ChiaWilliam Wood IIIWells W. WuLinda ZukleyJe-Nie PhueKevin G. BeckerRong-Fong ShenLuigi FerrucciNan-ping WengA diverse T cell receptor (TCR) repertoire is essential for protection against a variety of pathogens, and TCR repertoire size is believed to decline with age. However, the precise size of human TCR repertoires, in both total and subsets of T cells, as well as their changes with age, are not fully characterized. We conducted a longitudinal analysis of the human blood TCRα and TCRβ repertoire of CD4+ and CD8+ T cell subsets using a unique molecular identifier–based (UMI-based) RNA-seq method. Thorough analysis of 1.9 × 108 T cells yielded the lower estimate of TCR repertoire richness in an adult at 3.8 × 108. Alterations of the TCR repertoire with age were observed in all 4 subsets of T cells. The greatest reduction was observed in naive CD8+ T cells, while the greatest clonal expansion was in memory CD8+ T cells, and the highest increased retention of TCR sequences was in memory CD8+ T cells. Our results demonstrated that age-related TCR repertoire attrition is subset specific and more profound for CD8+ than CD4+ T cells, suggesting that aging has a more profound effect on cytotoxic as opposed to helper T cell functions. This may explain the increased susceptibility of older adults to novel infections.https://doi.org/10.1172/JCI158122Aging |
| spellingShingle | Xiaoping Sun Thomas Nguyen Achouak Achour Annette Ko Jeffrey Cifello Chen Ling Jay Sharma Toyoko Hiroi Yongqing Zhang Chee W. Chia William Wood III Wells W. Wu Linda Zukley Je-Nie Phue Kevin G. Becker Rong-Fong Shen Luigi Ferrucci Nan-ping Weng Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets The Journal of Clinical Investigation Aging |
| title | Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets |
| title_full | Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets |
| title_fullStr | Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets |
| title_full_unstemmed | Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets |
| title_short | Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets |
| title_sort | longitudinal analysis reveals age related changes in the t cell receptor repertoire of human t cell subsets |
| topic | Aging |
| url | https://doi.org/10.1172/JCI158122 |
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