Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells
Abstract
To explore whether any co-stimulatory receptor(s) for TCR signaling is involved in the age-associated decline in T-cell function, we analyzed changes in these receptors in freshly isolated mouse CD4(+) T cells during aging. Both the mRNA and protein expression levels of CTLA-4 and PD-1, negative co-stimulatory receptors, increase with aging. No such changes are observed for CD28, a positive regulatory receptor. PD-1 is highly expressed on the surface of old, but not young, mouse T cells, while the level of surface-expressed CTLA-4 is very low regardless of age. PD-1 is preferentially expressed on the surface of effector-memory (CD44(hi)CD62L(lo)) T cells, a subset that increases with aging. CD4(+)PD-1(+) T cells from old mice exhibit proliferative hyporesponsiveness. These results suggest that the up-regulation of surface-expressed PD-1 may cause the age-dependent functional decline in effector-memory T cells.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
An increase in the number of exhausted T cells is another immunological feature of adaptive immune ageing.
“Another immunological feature of adaptive immune ageing is the increase in the number of exhausted T cells, characterized by the expression of inhibitory receptor molecules (for example, PD1 and TIM3), decreased proliferative capacity and decreased effector functions118,119.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [119]
The citation lists haven’t been fetched yet
References 23 · Cited by 72
- Authors
- Shimada, Y., Hayashi, M., Nagasaka, Y., Ohno-Iwashita, Y., & Inomata, M.
- Affiliations
- Tokyo Metropolitan Institute of Gerontology (JP)
- Corresponding author
- Inomata, Mitsushi
- ORCID
- Hayashi, Masami
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 44
- Issue
- 8
- Pages
- 517-522
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2037764914
- Cited by
- 72
- References
- 23
- Citations by year
- 2025: 3 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 11 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 4
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- PD-1, CTLA-4, CD28, T cell senescence, CD4+ T cells, effector memory T cells, T cell receptor signaling, immunosenescence
- MeSH terms
- Aging, Animals, Antigens, Surface, Immunologic Memory, Male, Mice, Inbred C57BL, Phenotype, Blotting, Western, Up-Regulation, T-Lymphocytes, Regulatory, Apoptosis Regulatory Proteins, Mice, Programmed Cell Death 1 Receptor
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 ›
Are you an author, or do you see a problem with this page? Request a review