Diversity and clonal selection in the human T-cell repertoire
Open accessAbstract
Significance: A decline in the diversity of the T-cell receptor repertoire owing to thymic involution has been implicated as causing defective immune responses in the elderly. By applying next-generation sequencing of replicate TCRB libraries from highly purified T-cell subsets, and using nonparametric statistical analysis, we obtain estimates of repertoire richness in the young adult that are higher than previously reported. Although contracting with age, the repertoire remains highly diverse. These data challenge the paradigm that thymic rejuvenation is needed to maintain diversity and prevent immune incompetence in the elderly. However, we observe an increasing inequality of clonal sizes with age even among naïve T cells. This clonal selection could result in biased and possibly autoreactive immune responses.
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The decline in the diversity of the repertoire is modest, as compared to the reduction of the thymic output.
“even though the decline in the diversity of the repertoire is modest, as compared to the reduction of the thymic output [335].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [335]
Despite their lower frequency, naïve T-cell repertoire richness declines only modestly in healthy elderly adults, by 2-5 fold compared with young adults.
“despite their lower frequency, the repertoire richness of the naïve T cells declines only modestly in healthy elderly adults, i.e., 2–5 fold if compared with that of young adults [80].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [80]
Ageing changes can include diminished T cell receptor diversity.
“These changes can include an involuted thymus235, fewer naive B and T cells236, diminished T cell receptor diversity237, higher susceptibility to T cell apoptosis238 and reduced expression of crucial receptors such as CD28 on cytotoxic CD8+ T cells239.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [237]
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- Authors
- Qi, Q., Liu, Y., Cheng, Y., Glanville, J., Zhang, D., Lee, J.-Y., Olshen, R. A., Weyand, C. M., Boyd, S. D., & Goronzy, J. J.
- Affiliations
- Divisions of aImmunology and Rheumatology, Department of Medicine and
- Stanford University (US)
- Genetics, and
- Departments of cPathology,
- Biostatistics,
- VA Palo Alto Health Care System (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-08-25
- Volume
- 111
- Issue
- 36
- Pages
- 13139-13144
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4246948
- OpenAlex
- W1973639800
- Cited by
- 755
- References
- 42
- Citations by year
- 2026: 60 · 2025: 69 · 2024: 58 · 2023: 58 · 2022: 86 · 2021: 92 · 2020: 62 · 2019: 70 · 2018: 64 · 2017: 53 · 2016: 43 · 2015: 39 · 2014: 1
- FWCI
- 20.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- National Tsing Hua University
- National Institutes of Health (AI057266, AI090019, AI044142, HL058000)
- National Institute on Aging (R01AG045779, R01AG015043)
- National Heart, Lung, and Blood Institute (P01HL058000, R01HL117913)
- National Institute of Allergy and Infectious Diseases (R01AI044142, R01AI108906, R56AI044142, U19AI090019, R01AI108891, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527, T32AR050942)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Physical Sciences › Engineering › Biomedical Engineering › Artificial Immune Systems Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- T cell receptor repertoire, clonal selection, naive T cells, memory T cells, thymic involution, homeostatic proliferation, clonality, Gini-Simpson index, CD4+ T cells, CD8+ T cells, immunosenescence
- MeSH terms
- Adult, Aged, Aging, Base Sequence, Cell Compartmentation, Clone Cells, Humans, Immunologic Memory, Receptors, Antigen, T-Cell, T-Lymphocytes, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, CD4-Positive T-Lymphocytes, Cytokines, CD8-Positive T-Lymphocytes, Complementarity Determining Regions, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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