Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1)
Abstract
Adaptive immunity necessitates the proliferation of lymphocytes. In the mouse, we have previously shown that antigen-experienced T cells that have lost their proliferative potential express the killer cell lectinlike receptor G1 (KLRG1). By using a newly generated monoclonal antibody specific for human KLRG1, we now demonstrate that expression of KLRG1 also identifies T cells in humans that are capable of secreting cytokines but that fail to proliferate after stimulation. Furthermore, our data show that proliferative incapacity of CD8 T cells correlates better with KLRG1 expression than with absence of the CD28 marker. In peripheral blood lymphocytes (PBLs) from healthy adult donors, KLRG1 was expressed on 44% +/- 14% of CD8 and 18% +/- 10% of CD4 T cells. KLRG1 expression was restricted to antigen-experienced T cells. Here, KLRG1(+) cells were preferentially found in the CCR7(-) effector T-cell pool. Besides T cells, a significant portion (approximately 50%) of human natural killer (NK) cells expressed KLRG1. Interestingly, these KLRG1(+) NK cells were found exclusively in the CD56(dim) NK-cell subset. Thus, the expression of KLRG1 identifies a subset of NK cells and antigen-experienced T cells in humans that lack proliferative capacity.
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The loss of CD28 occurs following cell proliferation, according to the observation that CD28− T cells have shorter telomeres than CD28+ cells.
“The loss of CD28 occurs following cell proliferation, according to the observation that the CD28− T cells have shorter telomeres than CD28+ cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [43]
These T cells do not express the co-stimulatory molecule CD28, required for the activation of T cells.
“These T cells do not express the co-stimulatory molecule CD28, required for the activation of T cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [43]
Late-stage memory senescent T-cells may also acquire new functions, such as suppressive activity, as demonstrated in vitro.
“Late-stage memory senescent T-cells may also acquire new functions, such as suppressive activity, as demonstrated in vitro.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [43]
CD28 seems a good biomarker of immunosenescence, as suggested by findings that late-differentiated CD8+/CD28− T cells tend to accumulate particularly in older people, frail or affected by age-related diseases.
“CD28 seems a good biomarker of immunosenescence, as further suggested by findings that late-differentiated CD8+/CD28− T cells tend to accumulate particularly in older people, frail or affected by age-related diseases.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [43]
Senescent T cells are producers of pro-inflammatory cytokines.
“In addition, they are producers of pro-inflammatory cytokines (17, 18, 41–47).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [43]
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- Authors
- Voehringer, D., Koschella, M., & Pircher, H.
- Affiliations
- University of Freiburg (DE)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2002-11-15
- Volume
- 100
- Issue
- 10
- Pages
- 3698-3702
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2075052419
- Cited by
- 352
- References
- 41
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 14 · 2023: 15 · 2022: 20 · 2021: 17 · 2020: 7 · 2019: 16 · 2018: 12 · 2017: 15 · 2016: 13 · 2015: 16 · 2014: 14 · 2013: 18 · 2012: 19
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- KLRG1, T cell proliferation, effector T cells, memory T cells, CD8+ T cells, CD4+ T cells, natural killer cells, CD56dim NK cells, CCR7, CD28, antigen-experienced T cells, cytokine production
- MeSH terms
- Antibodies, Monoclonal, Flow Cytometry, Humans, Immunologic Memory, Killer Cells, Natural, Lymphocyte Activation, Receptors, Immunologic, T-Lymphocytes, Trans-Activators, Immunophenotyping, T-Lymphocyte Subsets, Lectins, C-Type
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