Advertisement

ResearchIn-Press PreviewAging Open Access | 10.1172/JCI158122

Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets

Xiaoping Sun,1 Thomas Nguyen,1 Achouak Achour,1 Annette Ko,1 Jeffrey Cifello,1 Chen Ling,1 Jay Sharma,1 Toyoko Hiroi,1 Yongqing Zhang,2 Chee W. Chia,3 William Wood III,2 Wells W. Wu,4 Linda Zukley,5 Je-Nie Phue,4 Kevin G. Becker,2 Rong-Fong Shen,4 Luigi Ferrucci,5 and Nan-ping Weng1

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Sun, X. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Nguyen, T. in: JCI | PubMed | Google Scholar |

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Achour, A. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Ko, A. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Cifello, J. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Ling, C. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Sharma, J. in: JCI | PubMed | Google Scholar |

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Hiroi, T. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Zhang, Y. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Chia, C. in: JCI | PubMed | Google Scholar |

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Wood III, W. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Wu, W. in: JCI | PubMed | Google Scholar |

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Zukley, L. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Phue, J. in: JCI | PubMed | Google Scholar |

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Becker, K. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Shen, R. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Ferrucci, L. in: JCI | PubMed | Google Scholar

1Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America

2Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, United States of America

3Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States of America

4Facility for Biotechnology Resources, Food and Drug Administration, Silver Spring, United States of America

5Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States of America

Find articles by Weng, N. in: JCI | PubMed | Google Scholar

Published June 16, 2022 - More info

J Clin Invest. https://doi.org/10.1172/JCI158122.
Copyright © 2022, Sun et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 16, 2022 - Version history
View PDF
Abstract

A diverse T cell receptor (TCR) repertoire is essential for protection against a variety of pathogens and T cell repertoire size is believed to decline with age. However, the precise size of human TCR repertoire in total and subsets of T cells, and 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 (UMI) based RNAseq method. Thorough analysis of 1.9 x 108 T cells yielded the lower estimate of TCR repertoire richness in an adult at 3.8 x 108. Alterations of TCR repertoire with age were observed in all four subsets of T cells. The greatest reduction was observed in naïve CD8+ T cells; 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 aging has a more profound impact on the cytotoxic than on the helper T cell functions. This may explain the increased susceptibility of older adults to the novel infections.

Graphical Abstract
graphical abstract
Supplemental material

View

Version history
  • Version 1 (June 16, 2022): In-Press Preview
Advertisement
Advertisement