Self-recognition drives the preferential accumulation of promiscuous CD4(+) T-cells in aged mice
Open accessAbstract
T-cell recognition of self and foreign peptide antigens presented in major histocompatibility complex molecules (pMHC) is essential for life-long immunity. How the ability of the CD4+ T-cell compartment to bind self- and foreign-pMHC changes over the lifespan remains a fundamental aspect of T-cell biology that is largely unexplored. We report that, while old mice (18–22 months) contain fewer CD4+ T-cells compared with adults (8–12 weeks), those that remain have a higher intrinsic affinity for self-pMHC, as measured by CD5 expression. Old mice also have more cells that bind individual or multiple distinct foreign-pMHCs, and the fold increase in pMHC-binding populations is directly related to their CD5 levels. These data demonstrate that the CD4+ T-cell compartment preferentially accumulates promiscuous constituents with age as a consequence of higher affinity T-cell receptor interactions with self-pMHC.
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Some clones selected during homeostatic proliferation may have higher self-affinity and promote autoreactive immunity in the elderly.
“some of these clones selected during homeostatic proliferation may have a higher affinity to self and therefore promote autoreactive immunity in the elderly”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Deshpande et al., 2015
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References 57 · Cited by 35
- Authors
- Deshpande, N. R., Parrish, H. L., & Kuhns, M. S.
- Affiliations
- University of Arizona (US)
- Corresponding author
- Kuhns, Michael S
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2015-07-14
- Volume
- 4
- Pages
- e05949-e05949
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4501121
- OpenAlex
- W1806320361
- Cited by
- 35
- References
- 57
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 8 · 2016: 3 · 2015: 1
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NIH) (BAA-NIAID-DAIT-NIHAI2010085)
- Pew Charitable Trusts
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- CD4+ T cells, T cell senescence, T cell receptor affinity, CD5 expression, major histocompatibility complex, T cell receptor repertoire, immunosenescence, peptide-MHC binding
- MeSH terms
- Animals, Autoantigens, CD4-Positive T-Lymphocytes, Self Tolerance, CD5 Antigens, Mice
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