Characterization of age‐associated exhausted CD 8+ T cells defined by increased expression of Tim‐3 and PD‐1

Lee, Kyoo‐A; Shin, Kwang‐Soo; Kim, Ga‐Young; Song, You Chan; Bae, Eun‐Ah; Kim, Il‐Kyu; Koh, Choong‐Hyun; Kang, Chang‐Yuil

doi:10.1111/acel.12435

Cited by 125T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmune Cell Function and Interaction

Characterization of age‐associated exhausted CD 8+ T cells defined by increased expression of Tim‐3 and PD‐1

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Lee, Kyoo‐A, Shin, Kwang‐Soo, Kim, Ga‐Young, Song, You Chan, Bae, Eun‐Ah, Kim, Il‐Kyu, Koh, Choong‐Hyun, Kang, Chang‐Yuil·2016·Aging Cell

DOI 10.1111/acel.12435PMC PMC4783346

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Abstract

Summary: Aging is accompanied by altered T‐cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 (PD‐1), in the T cells of aged mice emphasize the importance of investigations into the relationship between T‐cell exhaustion and aging‐associated immune dysfunction. In this study, we demonstrate that T‐cell immunoglobulin mucin domain‐3 (Tim‐3), another exhaustion marker, is up‐regulated on aged T cells, especially CD 8+ T cells. Tim‐3‐expressing cells also produced PD‐1, but Tim‐3+PD‐1+ CD 8+ T cells had a distinct phenotype that included the expression of CD 44 and CD 62L, from Tim‐3−PD‐1+ cells. Tim‐3+PD‐1+ CD 8+ T cells showed more evident properties associated with exhaustion than Tim‐3−PD‐1+ CD 8+ T cells: an exhaustion‐related marker expression profile, proliferative defects following homeostatic or TCR stimulation, and altered production of cytokines. Interestingly, these cells produced a high level of IL‐10 and induced normal CD 8+ T cells to produce IL‐10, which might contribute to immune dysregulation in aged mice. The generation of Tim‐3‐expressing CD 8+ T cells in aged mice seems to be mediated by encounters with antigens but not by specific infection, based on their high expression of CD 49d and their unbiased TCR Vβ usage. In conclusion, we found that a CD 8+ T‐cell population with age‐associated exhaustion was distinguishable by its expression of Tim‐3. These results provide clues for understanding the alterations that occur in T‐cell populations with age and for improving dysfunctions related to the aging of the immune system.

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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.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [118]

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Authors: Lee, K., Shin, K., Kim, G., Song, Y. C., Bae, E., Kim, I., Koh, C., & Kang, C.
Affiliations: Seoul National University (KR)
Laboratory of Immunology Research Institute of Pharmaceutical Sciences College of Pharmacy Seoul National University 1 Gwanak‐ro, Gwanak‐gu Seoul 151‐742 Korea
Corresponding author: Kang, Chang‐Yuil
ORCID: Kim, Ga‐Young
Song, You Chan
Bae, Eun‐Ah
Kim, Il‐Kyu
Koh, Choong‐Hyun
Kang, Chang‐Yuil
Venue: Aging Cell
Publisher: Wiley
Published: 2016-01-10
Volume: 15
Issue: 2
Pages: 291-300
ISSN: 1474-9718 (ISSN-L)
1474-9726
DOI: 10.1111/acel.12435
PMC: PMC4783346
OpenAlex: W2233554134
Cited by: 125
References: 40
Citations by year: 2026: 14 · 2025: 18 · 2024: 18 · 2023: 11 · 2022: 14 · 2021: 13 · 2020: 12 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 4
FWCI: 5.05
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Aging Cell (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Research Foundation
Ministry of Health and Welfare
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Keywords: T cell exhaustion, CD8+ T cells, TIM-3, PD-1, aging, immunosenescence, inhibitory receptors, IL-10, CD44, L-selectin, CD49d, TCR Vbeta usage, T cell proliferation, cytokine production, aged mice
MeSH terms: Hepatitis A Virus Cellular Receptor 2, Aging, Animals, CD8-Positive T-Lymphocytes, Mice, Programmed Cell Death 1 Receptor

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Characterization of age‐associated exhausted CD 8+ T cells defined by increased expression of Tim‐3 and PD‐1

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