Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus

Yager, Eric J.; Ahmed, Mushtaq; Lanzer, Kathleen; Randall, Troy D.; Woodland, David L.; Blackman, Marcia A.

doi:10.1084/jem.20071140

Cited by 490T-cell and B-cell ImmunologyInfluenza Virus Research StudiesImmunotherapy and Immune Responses

Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus

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Yager, Eric J., Ahmed, Mushtaq, Lanzer, Kathleen, Randall, Troy D., Woodland, David L., Blackman, Marcia A.·2008·The Journal of Experimental Medicine

DOI 10.1084/jem.20071140PMC PMC2275391

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Abstract

A diverse T cell repertoire is essential for a vigorous immune response to new infections, and decreasing repertoire diversity has been implicated in the age-associated decline in CD8 T cell immunity. In this study, using the well-characterized mouse influenza virus model, we show that although comparable numbers of CD8 T cells are elicited in the lung and lung airways of young and aged mice after de novo infection, a majority of aged mice exhibit profound shifts in epitope immunodominance and restricted diversity in the TCR repertoire of responding cells. A preferential decline in reactivity to viral epitopes with a low naive precursor frequency was observed, in some cases leading to “holes” in the T cell repertoire. These effects were also seen in young thymectomized mice, consistent with the role of the thymus in maintaining naive repertoire diversity. Furthermore, a decline in repertoire diversity generally correlated with impaired responses to heterosubtypic challenge. This study formally demonstrates in a mouse infection model that naturally occurring contraction of the naive T cell repertoire can result in impaired CD8 T cell responses to known immunodominant epitopes and decline in heterosubtypic immunity. These observations have important implications for the design of vaccine strategies for the elderly.

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Mice have a smaller starting repertoire and functional holes have been described with age.
“This is in contrast to mice, which have a smaller repertoire to start with and functional holes have been described with age”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Yager et al., 2008

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Authors: Yager, E. J., Ahmed, M., Lanzer, K., Randall, T. D., Woodland, D. L., & Blackman, M. A.
Affiliations: Trudeau Institute (US)
ORCID: Yager, Eric J.
Lanzer, Kathleen
Randall, Troy D.
Blackman, Marcia A.
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2008-03-10
Volume: 205
Issue: 3
Pages: 711-723
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.20071140
PMC: PMC2275391
OpenAlex: W2140058614
Cited by: 490
References: 80
Citations by year: 2026: 23 · 2025: 22 · 2024: 15 · 2023: 29 · 2022: 19 · 2021: 36 · 2020: 32 · 2019: 30 · 2018: 17 · 2017: 23 · 2016: 29 · 2015: 21 · 2014: 27 · 2013: 29 · 2012: 44
FWCI: 13.07
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Funders: National Institute on Aging (F32AG029010, R03AG022175, F23 AG029010)
National Institute of Allergy and Infectious Diseases (T32-AI49823, T32AI049823)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: T cell repertoire diversity, immunosenescence, CD8+ T cells, influenza virus, thymectomy, heterosubtypic immunity, T cell receptor repertoire, aged mice
MeSH terms: Aging, Animals, Antigenic Variation, Antigens, Viral, Female, Immune Tolerance, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Nucleoproteins, Influenza A virus, RNA-Dependent RNA Polymerase, T-Lymphocytes, Thymectomy, Viral Core Proteins, Viral Proteins, Immunodominant Epitopes, RNA-Binding Proteins, Receptors, Antigen, T-Cell, alpha-beta, Mice, Knockout, CD8-Positive T-Lymphocytes, Models, Immunological, Nucleocapsid Proteins, Genes, T-Cell Receptor beta, Mice, Precursor Cells, T-Lymphoid

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Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus

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