Cited by 72T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersGenetics, Aging, and Longevity in Model Organisms

Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells

Shimada, Yukiko, Hayashi, Masami, Nagasaka, Yasuhiko, Ohno-Iwashita, Yoshiko, Inomata, Mitsushi·2009·Experimental Gerontology

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.

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Crossref · 10.1016/j.exger.2009.05.003

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  • 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.”

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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
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

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